http://compbio.biosci.uq.edu.au/mediawiki/api.php?action=feedcontributions&user=Antonlord&feedformat=atomMDWiki - User contributions [en]2024-03-29T01:23:13ZUser contributionsMediaWiki 1.39.6http://compbio.biosci.uq.edu.au/mediawiki/index.php?title=ProteinAssignment2008&diff=10995ProteinAssignment20082008-07-03T15:06:08Z<p>Antonlord: /* Winter vacation scholarship */</p>
<hr />
<div>__NOTOC__<br />
<br />
Below there are pages provided which contain tables for our target proteins that summarize important information and links to databases.<br />
When you have formed groups and chosen your target protein, claim the target by adding your names into the protein assignment table below.<br />
<br />
=== Protein structure and sequences ===<br />
[http://compbio.chemistry.uq.edu.au/bmmg/thomas/08biol3004/08targets_table1.html Target PDB Table] contains links to stucture and sequence data.<br />
<br />
=== Human orthologs of target proteins ===<br />
[http://compbio.chemistry.uq.edu.au/bmmg/thomas/08biol3004/08targets_table2.html Target Blast and Symatlas Table] contains preset Blast search and links to functional data of human and mouse orthologs.<br />
<br />
<br />
<br />
'''Please choose from the following targets:'''<br />
<br />
high priority: 2, 5, 7, 9, 10, 11, 13, 18, 20, 21, 22<br><br />
alternative targets: 1, 12<br><br />
do '''not''' initially choose: 3, 4, 6, 8, 14, 15, 16, 17, 19<br />
<br />
<br />
=== Protein Assignment Table ===<br />
{| border="1" cellspacing="0" cellpadding="5" <br />
! target number<br />
! PDB code<br />
! protein name<br />
! investigators<br />
|- <br />
| 16<br />
| 3c5hA<br />
| glucocorticoid receptor DNA binding factor 1<br />
| Elizabeth Skippington, Mittchell Stanton-Cook, Thomas Huber<br />
|-<br />
| 18<br />
| 2cfsA<br />
| Pyridoxal (pyridoxine, vitamin B6) phosphatase<br />
| Yong Ming Lim, Du Guoqing, Sitoh Kheng Wai<br />
|- <br />
| 5<br />
| 2opw<br />
| Phytanoyl-CoA dioxygenase domain containing 1 isoform a<br />
| Eleanor McDonald, Liam Coulthard and Daniel Foskey<br />
|-<br />
| 7<br />
| 2ph1A<br />
| [[nucleotide binding protein 2 (MinD homolog, E.coli)]]<br />
| Mo Zhao, Siowwei Lee, Kenn Lu<br />
|- <br />
| 13<br />
| 2pbl<br />
| [[Arylformamidase]]<br />
| Basma Al Alaiwat, Sebastian Mynott, Thomas Parker<br />
|-<br />
|-]<br />
| 22<br />
| 3b5qA<br />
| [[Arylsulfatase K]] <br />
| Darshani Rupasinghe, Natasha Ferber<br />
|<br />
|-<br />
| 9<br />
| 2nxf<br />
| [[hypothetical protein LOC56985]] <br />
| Ivana Ferreira, Connor Skennerton, Nuwan Dahanayake<br />
|-<br />
| 21<br />
| 2ijz<br />
| [[Aspartyl Aminopeptidase]] <br />
| Luke Budianto Ishak, Krishna-Lila Shastri, Teng Meng Hua<br />
|- <br />
| 11<br />
| 2ece<br />
| [[Selenium binding protein]]<br />
| Lopson Kebapetswe, Robert O'Malley<br />
|-<br />
| 20<br />
| 2qq5<br />
| [[dehydrogenase/reductase (SDR family) member 1]]<br />
| Anton Lord, Charlie Brunello and Matthew Lovell<br />
|-<br />
| 1<br />
| 2qgnA <br />
| [[tRNA isopentenyltransferase 1]] <br />
| Jinhsien Choo, Emilyn Tan and Ana Lei <br />
|}<br />
<br />
=== Winter vacation scholarship ===<br />
Please indicate if you're interested to be considered for the winter vacation scholarship to complete your work for publication. This will have no influence on the project mark!<br />
<br />
{| border="1" cellspacing="0" cellpadding="5" <br />
! name<br />
! protein name<br />
! keen and available for scholarship<br />
|- <br />
|Elizabeth Skippington<br />
|glucocorticoid receptor DNA binding factor 1<br />
| yes<br />
<br />
|- <br />
|Basma Al Alaiwat, Sebastian Mynott<br />
|Arylformamidase<br />
| yes<br />
<br />
|- <br />
|Ivana Ferreira, Connor Skennerton<br />
|hypothetical protein LOC56985<br />
| yes<br />
<br />
|- <br />
|Anton Lord<br />
|dehydrogenase/reductase (SDR family) member 1<br />
| yes<br />
|}<br />
<br />
<br />
<br />
<br />
<br />
--[[User:ThomasHuber|ThomasHuber]] 17:00, 24 April 2008 (EST)</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=ProteinAssignment2008&diff=10994ProteinAssignment20082008-07-03T15:05:29Z<p>Antonlord: /* Winter vacation scholarship */</p>
<hr />
<div>__NOTOC__<br />
<br />
Below there are pages provided which contain tables for our target proteins that summarize important information and links to databases.<br />
When you have formed groups and chosen your target protein, claim the target by adding your names into the protein assignment table below.<br />
<br />
=== Protein structure and sequences ===<br />
[http://compbio.chemistry.uq.edu.au/bmmg/thomas/08biol3004/08targets_table1.html Target PDB Table] contains links to stucture and sequence data.<br />
<br />
=== Human orthologs of target proteins ===<br />
[http://compbio.chemistry.uq.edu.au/bmmg/thomas/08biol3004/08targets_table2.html Target Blast and Symatlas Table] contains preset Blast search and links to functional data of human and mouse orthologs.<br />
<br />
<br />
<br />
'''Please choose from the following targets:'''<br />
<br />
high priority: 2, 5, 7, 9, 10, 11, 13, 18, 20, 21, 22<br><br />
alternative targets: 1, 12<br><br />
do '''not''' initially choose: 3, 4, 6, 8, 14, 15, 16, 17, 19<br />
<br />
<br />
=== Protein Assignment Table ===<br />
{| border="1" cellspacing="0" cellpadding="5" <br />
! target number<br />
! PDB code<br />
! protein name<br />
! investigators<br />
|- <br />
| 16<br />
| 3c5hA<br />
| glucocorticoid receptor DNA binding factor 1<br />
| Elizabeth Skippington, Mittchell Stanton-Cook, Thomas Huber<br />
|-<br />
| 18<br />
| 2cfsA<br />
| Pyridoxal (pyridoxine, vitamin B6) phosphatase<br />
| Yong Ming Lim, Du Guoqing, Sitoh Kheng Wai<br />
|- <br />
| 5<br />
| 2opw<br />
| Phytanoyl-CoA dioxygenase domain containing 1 isoform a<br />
| Eleanor McDonald, Liam Coulthard and Daniel Foskey<br />
|-<br />
| 7<br />
| 2ph1A<br />
| [[nucleotide binding protein 2 (MinD homolog, E.coli)]]<br />
| Mo Zhao, Siowwei Lee, Kenn Lu<br />
|- <br />
| 13<br />
| 2pbl<br />
| [[Arylformamidase]]<br />
| Basma Al Alaiwat, Sebastian Mynott, Thomas Parker<br />
|-<br />
|-]<br />
| 22<br />
| 3b5qA<br />
| [[Arylsulfatase K]] <br />
| Darshani Rupasinghe, Natasha Ferber<br />
|<br />
|-<br />
| 9<br />
| 2nxf<br />
| [[hypothetical protein LOC56985]] <br />
| Ivana Ferreira, Connor Skennerton, Nuwan Dahanayake<br />
|-<br />
| 21<br />
| 2ijz<br />
| [[Aspartyl Aminopeptidase]] <br />
| Luke Budianto Ishak, Krishna-Lila Shastri, Teng Meng Hua<br />
|- <br />
| 11<br />
| 2ece<br />
| [[Selenium binding protein]]<br />
| Lopson Kebapetswe, Robert O'Malley<br />
|-<br />
| 20<br />
| 2qq5<br />
| [[dehydrogenase/reductase (SDR family) member 1]]<br />
| Anton Lord, Charlie Brunello and Matthew Lovell<br />
|-<br />
| 1<br />
| 2qgnA <br />
| [[tRNA isopentenyltransferase 1]] <br />
| Jinhsien Choo, Emilyn Tan and Ana Lei <br />
|}<br />
<br />
=== Winter vacation scholarship ===<br />
Please indicate if you're interested to be considered for the winter vacation scholarship to complete your work for publication. This will have no influence on the project mark!<br />
<br />
{| border="1" cellspacing="0" cellpadding="5" <br />
! name<br />
! protein name<br />
! keen and available for scholarship<br />
|- <br />
|Elizabeth Skippington<br />
|glucocorticoid receptor DNA binding factor 1<br />
| yes<br />
<br />
|- <br />
|Basma Al Alaiwat, Sebastian Mynott<br />
|Arylformamidase<br />
| yes<br />
<br />
|- <br />
|Ivana Ferreira, Connor Skennerton<br />
|hypothetical protein LOC56985<br />
| yes<br />
<br />
|- <br />
|Anton Lord<br />
|Dehydrogenase reductase SDR family 1<br />
| yes<br />
|}<br />
<br />
<br />
<br />
<br />
<br />
--[[User:ThomasHuber|ThomasHuber]] 17:00, 24 April 2008 (EST)</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Conclusion&diff=10445DHRS1 Conclusion2008-06-09T23:44:53Z<p>Antonlord: </p>
<hr />
<div>Through comparison of DHRS1 against proteins with similar structure it was possible to identify several conserved regions that are important in the folding and function of HSDR1.<br />
<br />
DHRS1 may reduce Glucose by using NAD(P) as an electron donor. Further kinetic studies with other likely substrates (sugars) are needed to confirm this. An [G-x(3)-G-x-G] motif that is a Characteristic co-enzyme binding fold may bind a substrate possibly glucose. Site directed mutagenasis and further kinetic studies will reveal the role of this motif, if any. Future studies of DHRS1 or similar related proteins may also lead to greater understanding of the SDR family and its biological importance or may potentially hold keys to better understanding of clinical problems like disease.<br />
<br />
DHRS1 has evolved over a long period of time, and the SDR family is found in all aspects of life. It has some highly conserved regions, such as LDVLV and the S-Y-K residues. The SDK superfamily can be split into many different families, the two most interesting to our target protein are classic SDR and extended SDR. Classic SDR form the predecessing family from which the extended SDR family originated. Our target protein is part of the extended SDR family. <br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Conclusion&diff=10422DHRS1 Conclusion2008-06-09T23:36:49Z<p>Antonlord: </p>
<hr />
<div>Through comparison of DHRS1 against proteins with similar structure it was possible to identify several conserved regions that are important in the folding and function of HSDR1.<br />
<br />
DHRS1 may reduce Glucose by using NAD(P) as an electron donor. Further kinetic studies with other likely substrates (sugars) are needed to confirm this. An [G-x(3)-G-x-G] motif that is a Characteristic co-enzyme binding fold may bind a substrate possibly glucose. Site directed mutagenasis and further kinetic studies will reveal the role of this motif, if any. Future studies of DHRS1 or similar related proteins may also lead to greater understanding of the SDR family and its biological importance or may potentially hold keys to better understanding of clinical problems like disease.<br />
<br />
DHRS1 has evolved over a long period of time, and is found in all aspects of life. It has some highly conserved regions, such as LDVLV and the S-Y-K residues. The SDK superfamily can be split into many different families, the two most interesting to our target protein are classic SDR and extended SDR. Classic SDR form the predecessing family from which the extended SDR family originated. Our target protein is part of the extended SDR family. <br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=9732DHRS1 Results2008-06-09T05:24:51Z<p>Antonlord: </p>
<hr />
<div><br />
<br />
==Phylogenetic Tree==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria. Blue branches show organisms of the anamalia kingdom, Black branches show organisms of the bacteria kingdom.<br />
<br />
Aedes aegypti and Schistosoma japonicum are both found in the anamalia kingdom, although are seperated on the graph. Both of these organisms are parasitic by nature.<br />
Aedes aegypti is commonly known as the yellow fever mosquito. Schistosoma japonicum is a parasite and one of the major infectious agents of schistosomiasis.<br />
<br />
The distribution of the branches in the tree is consistent with full organism genome taxonomic distribution, for example the prokaryotes are grouped together, and the eukaryotes are grouped together, with one distinct exception, Ades aegypti.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Clustal Alignment==<br />
<br />
Clustal alignment shows that Homo_sapiens_SDR_family_1 (an exact match for our target protein) with regards to <br />
protein sequence, contains all eight key residues (locations 117 - 121, 195,209 and 213). It also contains a <br />
sequence K-[A,S]-F-W-E-x-P-A-S at location 138 - 146 which is conserved only between land based animals.<br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
The N-terminus region of the clustal alignment shows the main difference between classical SDR's and extended SDR's. There is a highly conserved tail (locatoin 280 - 360) which appears only in some of the results aligned. As our target sequence is in the extended SDR family, most of the sequences aligned are also in the extended SDR family.<br />
<br />
[[Image:2qq5align2.png|framed|'''Figure 2'''<BR>Clustal Alignment of the N-terminus region of the target protein|none]]<BR><br />
<br />
==Structure==<br />
[[Image:chain.jpg|framed|'''Figure 6'''<BR>Sequence details of DHRS1 showing alpha helices and beta sheet in relation to amino acid sequence. Also showing a region of code 22 residues long that was not crystallized. Taken from the Protein Data Bank.|none]]<BR><br />
<br />
[[Image:pretty.png|framed|'''Figure 2'''<BR>Cartoon of a single DHRS1 unit with different structural features highlighted in different colours. |none]]<BR><br />
<br />
A single monomeric unit of DHRS1 contains 10 α helices 1 central β-sheet region consisting of 7 strands. It is thought to exist biologically as a dimer.<br />
<br />
DHRS1 has highly conserved structure compared across the SDR family.<br />
<br />
The SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised by a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P), residue 163 in the sequence above. It is part of a larger motif [S-x(12)-Y-x(3)-K] (residues 150-167)that includes two other residues (Serine, Lysine) involved in binding NAD(P) (Wu Q, et al 2001) This catalytic triad is located in a deep hydrophobic pocket.<br />
<br />
There are more highly conserved motifs including a [G-x(3)-G-x-G] (residues 14-20) that is part of a possible co-enzyme binding site and [LDVLV] (residues 86-90) involved in the initial folding of the protein (Wu Q, et al 2001). It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. <br />
<br />
[[Image:hydrophobicDHRS1.png|framed|'''Figure 2'''<BR>Electrostatic potential surface map of HSDR1 with the hydrophobic pocket containg the S-Y-K catalytic triad. |none]]<BR><br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 3'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with 3-Oxoacyl-(Acyl-Carrier-protien)reductase (green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
DALI server was used to perform a structural alignment. There where many highly significant hits some from the SDR Family and all hits whre from the Super Family; NAD(P)-binding Rossmann-fold domain proteins (Table 1).<br />
<br />
Comparison of DHRS1 to 3-Oxoacyl-(Acyl-Carrier-protien)reductase its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices, all of which are very closely aligned. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 0.7-3 Angstroms (fig 3).<br />
<br />
Futher comparison with other related protiens from the DALI structural alignment (Table 1), notably all of the glucose dehydrogenases and the other member of the SDR family SDR4 show this pattern to continue.<br />
<br />
[[Image:alighn 2uved catalytic site.png|framed|'''Figure 4'''<BR>Close in view of the catalytic triad (S-Y-K)from the alignment 2uvd and DHRS1. Showing the difference in the positions of the key residues. |none]]<BR><br />
<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search. Z = standard deviations above that expected. Z < 2.0 means no significant similarity.'''<br />
No: Chain Z nres %id Description<br />
1: 2qq5-A 48.1 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=9731DHRS1 Results2008-06-09T05:20:44Z<p>Antonlord: /* Results/Evolution */</p>
<hr />
<div>[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]<br />
<BR><br />
<BR><br />
[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
<br />
<br />
==Phylogenetic Tree==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria. Blue branches show organisms of the anamalia kingdom, Black branches show organisms of the bacteria kingdom.<br />
<br />
Aedes aegypti and Schistosoma japonicum are both found in the anamalia kingdom, although are seperated on the graph. Both of these organisms are parasitic by nature.<br />
Aedes aegypti is commonly known as the yellow fever mosquito. Schistosoma japonicum is a parasite and one of the major infectious agents of schistosomiasis.<br />
<br />
The distribution of the branches in the tree is consistent with full organism genome taxonomic distribution, for example the prokaryotes are grouped together, and the eukaryotes are grouped together, with one distinct exception, Ades aegypti.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Clustal Alignment==<br />
<br />
Clustal alignment shows that Homo_sapiens_SDR_family_1 (an exact match for our target protein) with regards to <br />
protein sequence, contains all eight key residues (locations 117 - 121, 195,209 and 213). It also contains a <br />
sequence K-[A,S]-F-W-E-x-P-A-S at location 138 - 146 which is conserved only between land based animals.<br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
The N-terminus region of the clustal alignment shows the main difference between classical SDR's and extended SDR's. There is a highly conserved tail (locatoin 280 - 360) which appears only in some of the results aligned. As our target sequence is in the extended SDR family, most of the sequences aligned are also in the extended SDR family.<br />
<br />
[[Image:2qq5align2.png|framed|'''Figure 2'''<BR>Clustal Alignment of the N-terminus region of the target protein|none]]<BR><br />
<br />
==Structure==<br />
[[Image:chain.jpg|framed|'''Figure 6'''<BR>Sequence details of DHRS1 showing alpha helices and beta sheet in relation to amino acid sequence. Also showing a region of code 22 residues long that was not crystallized. Taken from the Protein Data Bank.|none]]<BR><br />
<br />
[[Image:pretty.png|framed|'''Figure 2'''<BR>Cartoon of a single DHRS1 unit with different structural features highlighted in different colours. |none]]<BR><br />
<br />
A single monomeric unit of DHRS1 contains 10 α helices 1 central β-sheet region consisting of 7 strands. It is thought to exist biologically as a dimer.<br />
<br />
DHRS1 has highly conserved structure compared across the SDR family.<br />
<br />
The SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised by a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P), residue 163 in the sequence above. It is part of a larger motif [S-x(12)-Y-x(3)-K] (residues 150-167)that includes two other residues (Serine, Lysine) involved in binding NAD(P) (Wu Q, et al 2001) This catalytic triad is located in a deep hydrophobic pocket.<br />
<br />
There are more highly conserved motifs including a [G-x(3)-G-x-G] (residues 14-20) that is part of a possible co-enzyme binding site and [LDVLV] (residues 86-90) involved in the initial folding of the protein (Wu Q, et al 2001). It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. <br />
<br />
[[Image:hydrophobicDHRS1.png|framed|'''Figure 2'''<BR>Electrostatic potential surface map of HSDR1 with the hydrophobic pocket containg the S-Y-K catalytic triad. |none]]<BR><br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 3'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with 3-Oxoacyl-(Acyl-Carrier-protien)reductase (green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
DALI server was used to perform a structural alignment. There where many highly significant hits some from the SDR Family and all hits whre from the Super Family; NAD(P)-binding Rossmann-fold domain proteins (Table 1).<br />
<br />
Comparison of DHRS1 to 3-Oxoacyl-(Acyl-Carrier-protien)reductase its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices, all of which are very closely aligned. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 0.7-3 Angstroms (fig 3).<br />
<br />
Futher comparison with other related protiens from the DALI structural alignment (Table 1), notably all of the glucose dehydrogenases and the other member of the SDR family SDR4 show this pattern to continue.<br />
<br />
[[Image:alighn 2uved catalytic site.png|framed|'''Figure 4'''<BR>Close in view of the catalytic triad (S-Y-K)from the alignment 2uvd and DHRS1. Showing the difference in the positions of the key residues. |none]]<BR><br />
<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search. Z = standard deviations above that expected. Z < 2.0 means no significant similarity.'''<br />
No: Chain Z nres %id Description<br />
1: 2qq5-A 48.1 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
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[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Discussion&diff=9727DHRS1 Discussion2008-06-09T05:01:13Z<p>Antonlord: /* Sequence */</p>
<hr />
<div>==Sequence==<br />
<br />
The Short chain dehydrogenase family has evolved over a long period of time and has two main forms, classical SDR and extended SDR. <br />
Classic SDR is primarily found in bacteria and is approximately 250 amino acids long and appears to have evolved first, extended SDR's are typically 350 amino acids long and have evolved later. The sequence identity for this family is low, approximately 15 to 20%, This is due to two main reasons, firstly the relatively low number of highly conserved sequences, for example only 4 regions, totaling 8 residues are involved in the ATP binding site, and even within these regions there is some variation of the specific residue, although it is heavily restrained to within the certain groups of amino acids with similar properties and is still almost always conserved to the same residue in these important sites. These sites are infrequent and most of the residues are variable without any significant change in structure or function. Secondly this is partially due to the age of the family and has lead to many point mutations, which have been incorporated over time when the mutation is not fatal to the organism. <br />
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One of the mutations incorporated over time is for a subgroup of the family including land based higher organisms such as humans, monkeys, dogs, cats and cows. This is identified by an inserted motif K-[A,S]-F-W-E-x-P-A-S at location 138 - 146. This region does not exist in the classic SDR family and shows variation in the extended family, although is completely conserved within organisms such as those named earlier. The extended SDR family includes some proteobacteria and all the sequences of the anamalia kingdom with the exception of Aedes aegypti. This subgroup suggests that the extended SDR family evolved from the classic SDR family and has continued to evolve. It also suggests that this family was incorporated into higher organisms after this evolution to the extended SDR. <br />
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Aedes aegypti was the only eukaryote which incorporated the classic SDR protein in our phylogenetic tree. It is possible that this is due to this particular organisms parasitic nature and this may have increased the oppertunity for lateral gene transfer to occur (Sherwood 2007). It is possible that this organism did not have the ability to process glucose prior to incorporating this gene from a transfer event and due to this event had a significant evolutionary advantage, causing this protein to be conserved in the organism after transfer.<br />
<br />
==Structure==<br />
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The SDR family have highly conserved structural features in particular the NAD(P) binding site, central β-strand and co-enzyme binding site. HSDR1 is representative of the family with all of the required structural elements. It has the usual S-Y<br />
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Structural alignments of HSDR1 with other members of the SDR family showed that the most closely structurally related proteins were all involved in reducing substrates (reductases). In particular Glucose reductases appeared frequently (Table 1). All of the protiens that had high structural similarity existed as dimers, tetramers or octamers, indicating that DHRS1 also exists as more than a monomer biologically. Most of the protiens in the SDR family act in tandem with co-enzymes and a highly conserved motif [G-x(3)-G-x-G] that is thought to be a co-enzyme binding site (Wu Q, et al 2001) is also present in DHRS1.<br />
<br />
DHRS1 has been crystallized to a resolution of 1.8 Å with an R-value of 0.159. This R-value however was achieved without recording a highly mobile region of 22 amino acids which covers over the NAD(P) binding site, and may act as a cap protecting the NAD(P) binding site when the enzyme is not in use. This flexible region also covers part of the co-enzyme binding site indicating that this region moves when the enzyme is biologically active.<br />
<br />
==Function==<br />
<br />
To date, functional studies of DHRS1 have been limited and inconclusive. However, appropriate hypothesises can be formulated by comparing both structural and evolutionary similarities between DHRS1 and other similar known proteins. Also, If similar proteins contain similar structural properties then it can be suggested that DHRS1 shares its function or at least has a similar function to these other proteins. <br />
<br />
DHRS1 is a member of the SDR family, which although shows low sequence homology, still has conserved domains. SDR family members can be sub-categorised into sub-families from motif similarities. Classical, extended, intermediate, divergent and complex, are all defined by a sequence motif(s). Studies relating to other similar sub-family proteins offer insight into roles of DHRS1. Classical SDR family members share the following: [ILV]TGx(3)[AG][FILV]Gx(3)[AS]x(2)[FILMV]x(3)Gx(2)[ILMV] which is found from V12 to L25 in DHRS1. [http://www.blackwell-synergy.com/doi/abs/10.1046/j.1432-1033.2002.03130.x| (Kallberg et al. 2002b)]. This suggest that it is a classical SDR. <br />
<br />
The most important conserved motif is the NAD/NADP (Nicotinamide adenine dinucleotide (phosphate)) binding site as this reserves its function. (F) NAD and NADP have roles in metabolism, whether it is fatty acid metabolism, energy metabolism or reductive biosynthesis. [http://www.liebertonline.com/doi/pdf/10.1089/ars.2007.1672?cookieSet=1| (Ying, W. 2008)] <br />
<br />
[[Image:align 2uvd.png|thumb|right|Figure 3<br />
Cartoon of DHRS1 (cyan/magenta) aligned with 3-Oxoacyl-(Acyl-Carrier-protien)reductase (green/red) the key catalytic Tyrosine residue is shown in as well.]]<BR> <br />
<br />
By comparing functions of other similar proteins, a hypothesis as to the role of DHRS1 can be made. 3-oxoacyl-(acyl-carrier-protein) reductase is also a member of the SDR protein family and it also has the conserved binding sequence S-Y-K, in its Rossman fold, which is a structural binding motif. It has a role in biological processes because it binds coenzyme NAD and catalyses the oxidation of D-glucose to D-beta-gluconolactone which is a step in the glucose metabolic pathway. [http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| (Zaccai N et al. 2008)] <br />
<br />
Structurally, the proteins are also similar (See Figure 3) and a blast search puts its e-value at 9e-023.<br />
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[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9725DHRS1 References2008-06-09T04:56:48Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes <br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis <br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions <br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium <br />
<BR><br />
*Price A, Zhang Y, Rock C, White S. (2001) Structure of beta-ketoacyl-[acyl carrier protein] reductase from Escherichia coli: negative cooperativity and its structural basis. Biochemistry 40 12772-12781 [[http://pubs.acs.org/cgi-bin/article.cgi/bichaw/2001/40/i43/html/bi010737g.html| Link]]<br />
<BR><br />
*Jonathan Sherwood (2007) Bacterial to Animal Gene Transfers Now Shown to be Widespread, with Implications for Evolution and Control of Diseases and Pests [[http://www.rochester.edu/news/show.php?id=2963 Link]]<br />
<BR><br />
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[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9724DHRS1 References2008-06-09T04:56:25Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes <br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis <br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions <br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium <br />
<BR><br />
*Price A, Zhang Y, Rock C, White S. (2001) Structure of beta-ketoacyl-[acyl carrier protein] reductase from Escherichia coli: negative cooperativity and its structural basis. Biochemistry 40 12772-12781 [[http://pubs.acs.org/cgi-bin/article.cgi/bichaw/2001/40/i43/html/bi010737g.html| Link]]<br />
<BR><br />
*Jonathan Sherwood (2007) Bacterial to Animal Gene Transfers Now Shown to be Widespread, with Implications for Evolution and Control of Diseases and Pests [[http://www.rochester.edu/news/show.php?id=2963 | Link]]<br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9723DHRS1 References2008-06-09T04:56:03Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes <br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis <br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions <br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium <br />
<BR><br />
*Price A, Zhang Y, Rock C, White S. (2001) Structure of beta-ketoacyl-[acyl carrier protein] reductase from Escherichia coli: negative cooperativity and its structural basis. Biochemistry 40 12772-12781 [[http://pubs.acs.org/cgi-bin/article.cgi/bichaw/2001/40/i43/html/bi010737g.html| Link]]<br />
<BR><br />
*Jonathan Sherwood (2007) Bacterial to Animal Gene Transfers Now Shown to be Widespread, with Implications for Evolution and Control of Diseases and Pests [[http://www.rochester.edu/news/show.php?id=2963| Link]]<br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9722DHRS1 References2008-06-09T04:55:37Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes <br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis <br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions <br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium <br />
<BR><br />
*Price A, Zhang Y, Rock C, White S. (2001) Structure of beta-ketoacyl-[acyl carrier protein] reductase from Escherichia coli: negative cooperativity and its structural basis. Biochemistry 40 12772-12781 [[http://pubs.acs.org/cgi-bin/article.cgi/bichaw/2001/40/i43/html/bi010737g.html| Link]]<br />
<BR><br />
*Jonathan Sherwood (2007) Bacterial to Animal Gene Transfers Now Shown to be Widespread, with Implications for Evolution and Control of Diseases and Pests [[http://www.rochester.edu/news/show.php| Link]]<br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Abstract&diff=9717DHRS1 Abstract2008-06-09T04:35:03Z<p>Antonlord: </p>
<hr />
<div>Short chain dehydrogenase/reductases (SDR) form a large protein super-family family which shares approximately a 15-20% sequence identity which consists of at least 63 members (Kallberg et al. 2002). These can be differentiated into two families, classical and extended SDR. We found these families to be present in all forms of life, and have roles including alcohol, aldehyde (Duester, 1996) and steroid (Lin et al. 2001) dehydrogenase as well as being involved in the “molecular link between nutrient signaling and plant hormone biosynthesis” (Cheng et al. 2002). <br />
<br />
We performed sequence, structural and functional analysis on our target protein (DRHS1) and found it to be part of the extended SDR family, found in humans that have evolved from classic SDR from bacteria, is found as a dimer and the majority of the closest related proteins reduce glucose.<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Abstract&diff=9716DHRS1 Abstract2008-06-09T04:34:31Z<p>Antonlord: </p>
<hr />
<div>Short chain dehydrogenase/reductases (SDR) form a large protein super-family family which shares approximately a 15-20% sequence identity which consists of at least 63 members (Kallberg et al. 2002). These can be differentiated into two families, classical and extended SDR. We found these families to be present in all forms of life, and have roles including alcohol, aldehyde (Duester, 1996) and steroid (Lin et al. 2001) dehydrogenase as well as being involved in the “molecular link between nutrient signaling and plant hormone biosynthesis” (Cheng et al. 2002). <br />
<br />
We performed sequence, structural and functional analysis on our target protein (DRHS1) and found it to be part of the extended SDR family, found in humans that appears to have evolved from classic SDR from bacteria, is found as a dimer and the majority of the closest related proteins reduce glucose.<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Method&diff=9714DHRS1 Method2008-06-09T04:30:47Z<p>Antonlord: /* TREE VIEW */</p>
<hr />
<div>==BLAST==<br />
<br />
The protein sequence for the SDR family member 1 protein being investigated was downloaded from the PDB site, using the accession code 2qq5. This was then iteratively searched in blastp using an offline, non redundant copy of the database produced on the 28th of April 2008.<br />
<br />
<br />
<br />
==MULTIPLE SEQUENCE ALIGNMENT==<br />
<br />
The results from the blast search were then screened and a selection was of these results were used for a multiple sequence alignment using ClustalX. This result was boostrapped using 1000 simulations and these values checked and more sequences were added to improve the resolution of specific branches. A bootstrapped phylogram was produced.<br />
<br />
==TREE VIEW==<br />
<br />
The results from ClustalX were imported into treeview and a phylogenetic tree was produced, with bootstrapping values attached, and then split into bacteria and anamalia kingdoms.<br />
<br />
==STRUCTURAL ALIGNMENT==<br />
<br />
The protien sequence from PDB (2qq5) was aligned aginst other known sequences for structural similarity using the Dali web server. The structure of the most structurally related protien (Oxoacyl-(Acyl-carrier-protien) reductase) was alighned against DHRS1 in 3D using Pymol.<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Method&diff=9713DHRS1 Method2008-06-09T04:30:38Z<p>Antonlord: /* MULTIPLE SEQUENCE ALIGNMENT */</p>
<hr />
<div>==BLAST==<br />
<br />
The protein sequence for the SDR family member 1 protein being investigated was downloaded from the PDB site, using the accession code 2qq5. This was then iteratively searched in blastp using an offline, non redundant copy of the database produced on the 28th of April 2008.<br />
<br />
<br />
<br />
==MULTIPLE SEQUENCE ALIGNMENT==<br />
<br />
The results from the blast search were then screened and a selection was of these results were used for a multiple sequence alignment using ClustalX. This result was boostrapped using 1000 simulations and these values checked and more sequences were added to improve the resolution of specific branches. A bootstrapped phylogram was produced.<br />
<br />
==TREE VIEW==<br />
<br />
The results from ClustalX were imported into treeview and a phylogenetic tree was produced, with bootstrapping values attached, and then split into bacteria and anamalia kingdoms<br />
<br />
==STRUCTURAL ALIGNMENT==<br />
<br />
The protien sequence from PDB (2qq5) was aligned aginst other known sequences for structural similarity using the Dali web server. The structure of the most structurally related protien (Oxoacyl-(Acyl-carrier-protien) reductase) was alighned against DHRS1 in 3D using Pymol.<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Abstract&diff=9712DHRS1 Abstract2008-06-09T04:27:44Z<p>Antonlord: </p>
<hr />
<div>Short chain dehydrogenase/reductases (SDR) form a large protein super-family family which shares approximately a 15-20% sequence identity which consists of at least 63 members (Kallberg et al. 2002). These can be differentiated into two families, classical and extended SDR. We found these families to be present in all forms of life, and have roles including alcohol, aldehyde (Duester, 1996) and steroid (Lin et al. 2001) dehydrogenase as well as being involved in the “molecular link between nutrient signaling and plant hormone biosynthesis” (Cheng et al. 2002). <br />
<br />
We performed sequence, structural and functional analysis on our target protein (DRHS1) and found it to be part of the extended SDR family, found in humans that appears to have evolved from classic SDR from bacteria, is found as a dimer and appears to reduce glucose.<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Abstract&diff=9710DHRS1 Abstract2008-06-09T04:27:28Z<p>Antonlord: </p>
<hr />
<div>Short chain dehydrogenase/reductases (SDR) form a large protein super-family family which shares approximately a 15-20% sequence identity which consists of at least 63 members (Kallberg et al. 2002). These can be differentiated into two families, classical and extended SDR. We found these families to be present in all forms of life, and have roles including alcohol, aldehyde (Duester, 1996) and steroid (Lin et al. 2001) dehydrogenase as well as being involved in the “molecular link between nutrient signaling and plant hormone biosynthesis”(Cheng et al. 2002). <br />
<br />
We performed sequence, structural and functional analysis on our target protein (DRHS1) and found it to be part of the extended SDR family, found in humans that appears to have evolved from classic SDR from bacteria, is found as a dimer and appears to reduce glucose.<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Abstract&diff=9709DHRS1 Abstract2008-06-09T04:27:15Z<p>Antonlord: </p>
<hr />
<div>Short chain dehydrogenase/reductases (SDR) form a large protein super-family family which shares approximately a 15-20% sequence identity which consists of at least 63 members (Kallberg et al. 2002). These can be differentiated into two families, classical and extended SDR. We found these families to be present in all forms of life, and have roles including alcohol, aldehyde (Duester, 1996) and steroid (Lin et al. 2001) dehydrogenase as well as being involved in the “molecular link between nutrient signaling and plant hormone biosynthesis”(Cheng et al. 2002). Our target protein (DHRS1) is an extended SDR found in humans.<br />
<br />
We performed sequence, structural and functional analysis on our target protein (DRHS1) and found it to be part of the extended SDR family, found in humans that appears to have evolved from classic SDR from bacteria, is found as a dimer and appears to reduce glucose.<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9699DHRS1 References2008-06-09T04:18:28Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes <br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis <br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions <br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium <br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9698DHRS1 References2008-06-09T04:17:58Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes <br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis [[http://pubs.acs.org/cgi-<br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions <br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium <br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Abstract&diff=9696DHRS1 Abstract2008-06-09T04:16:50Z<p>Antonlord: </p>
<hr />
<div>Short chain dehydrogenase/reductases (SDR) form a large protein super-family family which shares approximately a 15-20% sequence identity which consists of at least 63 members (Kallberg et al. 2002). These can be differentiated into two families, classical and extended SDR. We found these families to be present in all forms of life, and have roles including alcohol, aldehyde (Duester, 1996) and steroid (Lin et al. 2001) dehydrogenase as well as being involved in the “molecular link between nutrient signaling and plant hormone biosynthesis”(Cheng et al. 2002). Our target protein (DHRS1) is an extended SDR found in humans.<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Abstract&diff=9694DHRS1 Abstract2008-06-09T04:16:24Z<p>Antonlord: </p>
<hr />
<div>Short chain dehydrogenase/reductases (SDR) form a large protein super-family family which shares approximately a 15-20% sequence identity which consists of at least 63 members (Kallberg et al. 2002). These can be differentiated into two families, classical and extended SDR. We found these families to be present in all forms of life, and have roles including alcohol, aldehyde (Duester, 1996) and steroid (Lin et al. 2001) dehydrogenase as well as being involved in the “molecular link between nutrient signaling and plant hormone biosynthesis”(Cheng et al. 2002). Our target protein (DRHS1) is an extended SDR found in humans.<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9693DHRS1 References2008-06-09T04:14:25Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes [[http://protsci.highwire.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis [[http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/1996/35/i38/abs/bi961176+.html| Link]]<br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions [[http://stke.sciencemag.org/cgi/content/abstract/plantcell;14/11/2723| Link]]<br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium [[http://cancerres.aacrjournals.org/cgi/content/abstract/61/4/1611| Link]]<br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9692DHRS1 References2008-06-09T04:11:08Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes [[http://protsci.highwire.org/cgi/content/abstract/11/3/636| Link]]<br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis [[http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/1996/35/i38/abs/bi961176+.html| Link]]<br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions [[http://stke.sciencemag.org/cgi/content/abstract/plantcell;14/11/2723| Link]]<br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium [[http://cancerres.aacrjournals.org/cgi/content/abstract/61/4/1611| Link]]<br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_References&diff=9689DHRS1 References2008-06-09T04:08:12Z<p>Antonlord: </p>
<hr />
<div>*Zaccai N, Carter L, Berrow N, Sainsbury s, Nettleship J, Walters T, Harlos K, Owens R, Wilson K, Stuart D, Esnouf R. (2008) Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution. Proteins. 70 (2) 562-567 [[http://www3.interscience.wiley.com/cgi-bin/fulltext/116322297/PDFSTART| Link]]<br />
<BR><br />
*Qihan Wu, Ming Xu, Chao Cheng, Zongxiang Zhou1, Yan Huang, Wei Zhao, Li Zeng, JianXu, Xuping Fu, Kang Ying, Yi Xie, YuminMao. (2002) Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 gene from human fetal brain. Molecular Biology Reports (28) 193–198<br />
<BR><br />
*Tramontano, A. (1998) Homology Modeling with Low Sequence Identity. Methods: A Companion to Methods in Enzymolgy. (14) 293-300.<br />
<BR><br />
*Edgar, A. (2002) Molecular cloning and tissue distribution of mammalian L-threonine 3-dehydrogenases. BMC Biochemistry (3) 19. [[http://www.biomedcentral.com/1471-2091/3/19| Link]]<br />
<BR><br />
*Kallberg, Y. Oppermann, U. Jörnvall, H. and Persson, B. (2002)a Short-chain Dehydrogenase/Reductase (SDR) Relationships: A Large Family With Eight Clusters Common to Human, Animal, and Plant Genomes. Protein Science (11) 636-641. [[http://www.proteinscience.org/cgi/content/full/11/3/636| Link]]<br />
<BR><br />
*Takahama, U. (1983) Redox Reactions between Kaempferol and Illuminate Chloroplasts. Plant Physiol. 71 (3) 598-601<br />
<BR><br />
*Ying, W. (2008) NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences. Antioxidants and Redox Signaling. (10) 2 179-206<br />
<BR><br />
*Kallberg, Y. Oppermann U. Jornvall, H. Persson B. (2002)b Short-chain Dehydrogenases/reductases (SDRs) Coenzyme-based Functional Assignments in Completed Genomes. European Jounal of Biochemistry. 269 4409-4417<br />
<BR><br />
*Yvonne Kallberg , Udo Oppermann, Hans Jörnvall and Bengt Persson, (2002), Short-chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes<br />
<BR><br />
*Gregg Duester (1996), Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis<br />
<BR><br />
*Wan-Hsing Cheng, Akira Endo, Li Zhou, Jessica Penney, Huei-Chi Chen, Analilia Arroyo, Patricia Leon, Eiji Nambara, Tadao Asami, Mitsunori Seo, Tomokazu Koshiba, and Jen Sheen (2002), A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions<br />
<BR><br />
*Biaoyang Lin, James T. White, Camari Ferguson, Shunyou Wang, Robert Vessella, Roger Bumgarner, Lawrence D. True, Leroy Hood and Peter S. Nelson (2001), Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium<br />
<BR><br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Discussion&diff=9664DHRS1 Discussion2008-06-09T03:38:36Z<p>Antonlord: </p>
<hr />
<div>==Sequence==<br />
<br />
The Short chain dehydrogenase family has evolved over a long period of time and has two main forms, classical SDR and extended SDR. <br />
Classic SDR is primarily found in bacteria and is approximately 250 amino acids long and appears to have evolved first, extended SDR's are typically 350 amino acids long and have evolved later. The sequence identity for this family is low, approximately 15 to 20%, This is due to two main reasons, firstly the relatively low number of highly conserved sequences, for example only 4 regions, totaling 8 residues are involved in the ATP binding site, and even within these regions there is some variation of the specific residue, although it is heavily restrained to within the certain groups of amino acids with similar properties and is still almost always conserved to the same residue in these important sites. These sites are infrequent and most of the residues are variable without any significant change in structure or function. Secondly this is partially due to the age of the family and has lead to many point mutations, which have been incorporated over time when the mutation is not fatal to the organism. <br />
<br />
One of the mutations incorporated over time is for a subgroup of the family including land based higher organisms such as humans, monkeys, dogs, cats and cows. This is identified by an inserted motif K-[A,S]-F-W-E-x-P-A-S at location 138 - 146. This region does not exist in the classic SDR family and shows variation in the extended family, although is completely conserved within organisms such as those named earlier. The extended SDR family includes some proteobacteria and all the sequences of the anamalia kingdom with the exception of Aedes aegypti. This subgroup suggests that the extended SDR family evolved from the classic SDR family and has continued to evolve. It also suggests that this family was incorporated into higher organisms after this evolution to the extended SDR. <br />
<br />
Aedes aegypti was the only eukaryote which incorporated the classic SDR protein in our phylogenetic tree. It is possible that this is due to this particular organisms parasitic nature and this may have increased the oppertunity for lateral gene transfer to occur. It is possible that this organism did not have the ability to process glucose prior to incorporating this gene from a transfer event and due to this event had a significant evolutionary advantage, causing this protein to be conserved in the organism after transfer.<br />
<br />
<br />
<br />
==Structure==<br />
<br />
The SDR family have highly conserved structural features in particular the NAD(P) binding site, central β-strand and co-enzyme binding site.<br />
<br />
Structural alignments with other members of the SDR family showed that the most closely structurally related proteins were all involved in reducing substrates (reductases). In particular Glucose reductases appeared frequently (Table 1). All of the protiens that had high structural similarity existed as dimers, tetramers or octamers, indicating that DHRS1 also exists as more than a monomer biologically. Most of the protiens in the SDR family act in tandem with co-enzymes and a highly conserved motif [G-x(3)-G-x-G] that is thought to be a co-enzyme binding site (Wu Q, et al 2001) is also present in DHRS1.<br />
<br />
DHRS1 has been crystallized to a resolution of 1.8 Å with an R-value of 0.159. This R-value however was achieved without recording a highly mobile region of 22 amino acids which covers over the NAD(P) binding site, and may act as a cap protecting the NAD(P) binding site when the enzyme is not in use. This flexible region also covers part of the co-enzyme binding site indicating that this region moves when the enzyme is biologically active.<br />
<br />
==Function==<br />
<br />
To date, functional studies of DHRS1 have been limited and inconclusive. However, some appropriate hypothesises can be formulated by comparing both structural and evolutionary similarities between DHRS1 and other similar known proteins. <br />
<br />
DHRS1 is a member of the SDR family, which although shows low sequence homology, still has conserved domains. SDR family members can be sub-categorised into sub-families from motif similarities. Classical, extended, intermediate, divergent and complex, are all defined by a sequence motif(s). This should mean that studies relating to other similar sub-family proteins should offer insight into roles of DHRS1. Classical SDR family members share the following: [ILV]TGx(3)[AG][FILV]Gx(3)[AS]x(2)[FILMV]x(3)Gx(2)[ILMV] which is found from V12 to L25 in DHRS1. [http://www.blackwell-synergy.com/doi/abs/10.1046/j.1432-1033.2002.03130.x| (Kallberg et al. 2002b)]. This suggest that it is a classical SDR. Kallberg <br />
<br />
The most important consevered motif is the NAD/NADP (Nicotinamide adenine dinucleotide (phosphate)) binding site as this reserves its function. (F) NAD and NADP as well as their variants have roles in metabolism, whether it is fatty acid metabolism, energy metabolism or reductive biosynthesis. [http://www.liebertonline.com/doi/pdf/10.1089/ars.2007.1672?cookieSet=1| (Ying, W. 2008)] <br />
<br />
<br />
<br />
<br />
By comparing the function of other similar proteins, a hypothesis as to the function of DHRS1 can be made. 3-oxoacyl-(acyl-carrier-protein) reductase is also a member of the SDR protein family <br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Discussion&diff=9663DHRS1 Discussion2008-06-09T03:38:09Z<p>Antonlord: /* Sequence */</p>
<hr />
<div>==Structure==<br />
<br />
The SDR family have highly conserved structural features in particular the NAD(P) binding site, central β-strand and co-enzyme binding site.<br />
<br />
Structural alignments with other members of the SDR family showed that the most closely structurally related proteins were all involved in reducing substrates (reductases). In particular Glucose reductases appeared frequently (Table 1). All of the protiens that had high structural similarity existed as dimers, tetramers or octamers, indicating that DHRS1 also exists as more than a monomer biologically. Most of the protiens in the SDR family act in tandem with co-enzymes and a highly conserved motif [G-x(3)-G-x-G] that is thought to be a co-enzyme binding site (Wu Q, et al 2001) is also present in DHRS1.<br />
<br />
DHRS1 has been crystallized to a resolution of 1.8 Å with an R-value of 0.159. This R-value however was achieved without recording a highly mobile region of 22 amino acids which covers over the NAD(P) binding site, and may act as a cap protecting the NAD(P) binding site when the enzyme is not in use. This flexible region also covers part of the co-enzyme binding site indicating that this region moves when the enzyme is biologically active.<br />
<br />
==Sequence==<br />
<br />
The Short chain dehydrogenase family has evolved over a long period of time and has two main forms, classical SDR and extended SDR. <br />
Classic SDR is primarily found in bacteria and is approximately 250 amino acids long and appears to have evolved first, extended SDR's are typically 350 amino acids long and have evolved later. The sequence identity for this family is low, approximately 15 to 20%, This is due to two main reasons, firstly the relatively low number of highly conserved sequences, for example only 4 regions, totaling 8 residues are involved in the ATP binding site, and even within these regions there is some variation of the specific residue, although it is heavily restrained to within the certain groups of amino acids with similar properties and is still almost always conserved to the same residue in these important sites. These sites are infrequent and most of the residues are variable without any significant change in structure or function. Secondly this is partially due to the age of the family and has lead to many point mutations, which have been incorporated over time when the mutation is not fatal to the organism. <br />
<br />
One of the mutations incorporated over time is for a subgroup of the family including land based higher organisms such as humans, monkeys, dogs, cats and cows. This is identified by an inserted motif K-[A,S]-F-W-E-x-P-A-S at location 138 - 146. This region does not exist in the classic SDR family and shows variation in the extended family, although is completely conserved within organisms such as those named earlier. The extended SDR family includes some proteobacteria and all the sequences of the anamalia kingdom with the exception of Aedes aegypti. This subgroup suggests that the extended SDR family evolved from the classic SDR family and has continued to evolve. It also suggests that this family was incorporated into higher organisms after this evolution to the extended SDR. <br />
<br />
Aedes aegypti was the only eukaryote which incorporated the classic SDR protein in our phylogenetic tree. It is possible that this is due to this particular organisms parasitic nature and this may have increased the oppertunity for lateral gene transfer to occur. It is possible that this organism did not have the ability to process glucose prior to incorporating this gene from a transfer event and due to this event had a significant evolutionary advantage, causing this protein to be conserved in the organism after transfer.<br />
<br />
==Function==<br />
<br />
To date, functional studies of DHRS1 have been limited and inconclusive. However, some appropriate hypothesises can be formulated by comparing both structural and evolutionary similarities between DHRS1 and other similar known proteins. <br />
<br />
DHRS1 is a member of the SDR family, which although shows low sequence homology, still has conserved domains. SDR family members can be sub-categorised into sub-families from motif similarities. Classical, extended, intermediate, divergent and complex, are all defined by a sequence motif(s). This should mean that studies relating to other similar sub-family proteins should offer insight into roles of DHRS1. Classical SDR family members share the following: [ILV]TGx(3)[AG][FILV]Gx(3)[AS]x(2)[FILMV]x(3)Gx(2)[ILMV] which is found from V12 to L25 in DHRS1. [http://www.blackwell-synergy.com/doi/abs/10.1046/j.1432-1033.2002.03130.x| (Kallberg et al. 2002b)]. This suggest that it is a classical SDR. Kallberg <br />
<br />
The most important consevered motif is the NAD/NADP (Nicotinamide adenine dinucleotide (phosphate)) binding site as this reserves its function. (F) NAD and NADP as well as their variants have roles in metabolism, whether it is fatty acid metabolism, energy metabolism or reductive biosynthesis. [http://www.liebertonline.com/doi/pdf/10.1089/ars.2007.1672?cookieSet=1| (Ying, W. 2008)] <br />
<br />
<br />
<br />
<br />
By comparing the function of other similar proteins, a hypothesis as to the function of DHRS1 can be made. 3-oxoacyl-(acyl-carrier-protein) reductase is also a member of the SDR protein family <br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Discussion&diff=8347DHRS1 Discussion2008-06-03T08:27:37Z<p>Antonlord: /* Sequence */</p>
<hr />
<div>==Structure==<br />
<br />
The SDR family have highly conserved structural features in particular the NAD(P) binding site, central β-strand and co-enzyme binding site.<br />
<br />
DHRS1 has been crystallized to a resolution of 1.8 Å with an R-value of 0.159. This R-value however was achieved without recording a highly mobile region of 22 amino acids which covers over the NAD(P) binding site, and may act as a cap locking the NAD(P) into the binding site (fig6).<br />
<br />
Structural alignments with other members of the SDR family showed that the most closely structurally related proteins where all involved in reducing substrates (reductases). In particular Glucose reductases appeared frequently (Table 1).<br />
<br />
==Sequence==<br />
<br />
The Short chain dehydrogenase family has evolved over a long period of time and has two main forms, classical SDR <br />
and extended SDR.<br />
<br />
Classic SDR is primarily found in bacteria and is approximately 250 amino acids long and appears to have evolved <br />
first, extended SDR's are typically 350 amino acids long and have evolved later. The sequence identity for this <br />
family is low, approdimately 15 to 20%, This is due to the age of the family and has lead to many point mutations, <br />
which have been incorporated over time when the mutation is not fatal to the organism.<br />
<br />
<br />
One of the mutations incorporated over time is for a subgroup of the family including land based higher organisms <br />
such as humans, monkeys, dogs, cats and cows. This is identified by an inserted motif K-[A,S]-F-W-E-x-P-A-S at <br />
location 138 - 146. This region does not exist in the classic SDR family and shows variation in the extended family, <br />
although is completely conserved within organisms such as those named earlier. The extended SDR family includes <br />
some proteobacteria and all the sequences of the anamalia kingdom with the exception of Aedes aegypti. This <br />
subgroup suggests that the extended SDR family evolved from the classic SDR family and has continued to evolve. It <br />
also suggests that this family was incorporated into higher organisms after this evolution to the extended SDR.<br />
<br />
Aedes aegypti was the only eukaryote which incorporated the classic SDR protein in our phylogenetic tree. It is possible that this is due to this particular organisms parasitic nature and this may have increased the oppertunity for lateral gene transfer to occur. It is possible that this organism did not have the ability to process glucose prior to incorporating this gene from a transfer event and due to this event had a significant evolutionary advantage, causing this protein to be conserved in the organism after transfer.<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8339DHRS1 Results2008-06-03T08:20:47Z<p>Antonlord: /* Results/Evolution */</p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
<br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria. Blue branches show organisms of the anamalia kingdom, Black branches show organisms of the bacteria kingdom.<br />
<br />
Aedes aegypti and Schistosoma japonicum are both found in the anamalia kingdom, although are seperated on the graph. Both of these organisms are parasitic by nature.<br />
Aedes aegypti is commonly known as the yellow fever mosquito. Schistosoma japonicum is a parasite and one of the major infectious agents of schistosomiasis.<br />
<br />
The distribution of the branches in the tree is consistent with full organism genome taxonomic distribution, for example the prokaryotes are grouped together, and the eukaryotes are grouped together, with one distinct exception, Ades aegypti.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Clustal Alignment==<br />
<br />
Clustal alignment shows that Homo_sapiens_SDR_family_1 (an exact match for our target protein) with regards to <br />
protein sequence, contains all eight key residues (locations 117 - 121, 195,209 and 213). It also contains a <br />
sequence K-[A,S]-F-W-E-x-P-A-S at location 138 - 146 which is conserved only between land based animals.<br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
The N-terminus region of the clustal alignment shows the main difference between classical SDR's and extended SDR's. There is a highly conserved tail (locatoin 280 - 360) which appears only in some of the results aligned. As our target sequence is in the extended SDR family, most of the sequences aligned are also in the extended SDR family.<br />
<br />
[[Image:2qq5align2.png|framed|'''Figure 2'''<BR>Clustal Alignment of the N-terminus region of the target protein|none]]<BR><br />
<br />
==Results/structure==<br />
[[Image:chain.jpg|framed|'''Figure 6'''<BR>Sequence details of DHRS1 showing alpha helices and beta sheet in relation to amino acid sequence. Also showing a region of code 22 residues long that was not crystallized. Taken from the Protein Data Bank.|none]]<BR><br />
<br />
[[Image:pretty.png|framed|'''Figure 2'''<BR>Cartoon of a single DHRS1 unit with different structural features highlighted in different colours. |none]]<BR><br />
<br />
A single monomeric unit of DHRS1 contains 10 α helices 1 central β-sheet region consisting of 7 strands. It is thought to exist biologically as a dimer.<br />
<br />
DHRS1 has highly conserved structure compared across the SDR family.<br />
<br />
The SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised by a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P). It is part of a larger motif [S-x(12)-Y-x(3)-K] that includes two other residues involved in binding NAD(P) (Wu Q, et al 2001).<br />
<br />
There are more highly conserved motifs including a [G-x(3)-G-x-G] that is part of a c0-enzyme binding site???? and [LDVLD] involved in the initial folding of the protein (Wu Q, et al 2001). It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. <br />
<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 3'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with 3-Oxoacyl-(Acyl-Carrier-protien)reductase (green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Comparison of DHRS1 to 3-Oxoacyl-(Acyl-Carrier-protien)reductase its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 0.7-3 Angstroms (fig 3).<br />
<br />
[[Image:alighn 2uved catalytic site.png|framed|'''Figure 4'''<BR>Close in view of the catalytic triad (S-Y-K)from the alignment 2uvd and DHRS1. Showing the difference in the positions of the key residues. |none]]<BR><br />
<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search. Z = standard deviations above that expected. Z < 2.0 means no significant similarity.'''<br />
No: Chain Z nres %id Description<br />
1: 2qq5-A 48.1 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Discussion&diff=8303DHRS1 Discussion2008-06-03T07:59:51Z<p>Antonlord: </p>
<hr />
<div>==Structure==<br />
HA! first<br />
<br />
Although the SDR family show low sequence identity (15-20%) they have highly conserved structural features in particular the NAD(P) binding site, central β-strand and co-enzyme binding site.<br />
<br />
DHRS1 has been crystallized to a resolution of 1.8 Å with an R-value of 0.159. This R-value however was achieved without recording a highly mobile region of 22 amino acids which covers over the NAD(P) binding site, and may act as a cap locking the NAD(P) into the binding site.<br />
<br />
Structural alignments with other members of the SDR family showed that the most closely structurally related proteins where all involved in reducing substrates (reductases). In particular Glucose reductases appeared frequently (Table 1). <br />
<br />
<br />
==Sequence==<br />
<br />
The Short chain dehydrogenase family has evolved over a long period of time and has two main forms, classical SDR <br />
and extended SDR.<br />
<br />
Classic SDR is primarily found in bacteria and is approximately 250 amino acids long and appears to have evolved <br />
first, extended SDR's are typically 350 amino acids long and have evolved later. The sequence identity for this <br />
family is low, approdimately 15 to 20%, This is due to the age of the family and has lead to many point mutations, <br />
which have been incorporated over time when the mutation is not fatal to the organism.<br />
<br />
<br />
One of the mutations incorporated over time is for a subgroup of the family including land based higher organisms <br />
such as humans, monkeys, dogs, cats and cows. This is identified by an inserted motif K-[A,S]-F-W-E-x-P-A-S at <br />
location 138 - 146. This region does not exist in the classic SDR family and shows variation in the extended family, <br />
although is completely conserved within organisms such as those named earlier. The extended SDR family includes <br />
some proteobacteria and all the sequences of the anamalia kingdom with the exception of Aedes aegypti. This <br />
subgroup suggests that the extended SDR family evolved from the classic SDR family and has continued to evolve. It <br />
also suggests that this family was incorporated into higher organisms after this evolution to the extended SDR.<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Discussion&diff=8298DHRS1 Discussion2008-06-03T07:58:21Z<p>Antonlord: /* Structure */</p>
<hr />
<div>==Structure==<br />
HA! first<br />
<br />
Although the SDR family show low sequence identity (15-20%) they have highly conserved structural features in particular the NAD(P) binding site, central β-strand and co-enzyme binding site.<br />
<br />
DHRS1 has been crystallized to a resolution of 1.8 Å with an R-value of 0.159. This R-value however was achieved without recording a highly mobile region of 22 amino acids which covers over the NAD(P) binding site, and may act as a cap locking the NAD(P) into the binding site.<br />
<br />
Structural alignments with other members of the SDR family showed that the most closely structurally related proteins where all involved in reducing substrates (reductases). In particular Glucose reductases appeared frequently (Table 1). <br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]<br />
<br />
==Sequence==<br />
<br />
The Short chain dehydrogenase family has evolved over a long period of time and has two main forms, classical SDR <br />
and extended SDR.<br />
<br />
Classic SDR is primarily found in bacteria and is approximately 250 amino acids long and appears to have evolved <br />
first, extended SDR's are typically 350 amino acids long and have evolved later. The sequence identity for this <br />
family is low, approdimately 15 to 20%, This is due to the age of the family and has lead to many point mutations, <br />
which have been incorporated over time when the mutation is not fatal to the organism.<br />
<br />
<br />
One of the mutations incorporated over time is for a subgroup of the family including land based higher organisms <br />
such as humans, monkeys, dogs, cats and cows. This is identified by an inserted motif K-[A,S]-F-W-E-x-P-A-S at <br />
location 138 - 146. This region does not exist in the classic SDR family and shows variation in the extended family, <br />
although is completely conserved within organisms such as those named earlier. The extended SDR family includes <br />
some proteobacteria and all the sequences of the anamalia kingdom with the exception of Aedes aegypti. This <br />
subgroup suggests that the extended SDR family evolved from the classic SDR family and has continued to evolve. It <br />
also suggests that this family was incorporated into higher organisms after this evolution to the extended SDR.</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8228DHRS1 Results2008-06-03T07:00:52Z<p>Antonlord: /* Clustal Alignment */</p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
<br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria. Blue branches show organisms of the anamalia kingdom, Black branches show organisms of the bacteria kingdom.<br />
<br />
Aedes aegypti and Schistosoma japonicum are both found in the anamalia kingdom, although are seperated on the graph. Both of these organisms are parasitic by nature.<br />
Aedes aegypti is commonly known as the yellow fever mosquito. Schistosoma japonicum is a parasite and one of the major infectious agents of schistosomiasis.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Clustal Alignment==<br />
<br />
Clustal alignment shows that Homo_sapiens_SDR_family_1 (an exact match for our target protein) with regards to <br />
protein sequence, contains all eight key residues (locations 117 - 121, 195,209 and 213). It also contains a <br />
sequence K-[A,S]-F-W-E-x-P-A-S at location 138 - 146 which is conserved only between land based animals.<br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
The N-terminus region of the clustal alignment shows the main difference between classical SDR's and extended SDR's. There is a highly conserved tail (locatoin 280 - 360) which appears only in some of the results aligned. As our target sequence is in the extended SDR family, most of the sequences aligned are also in the extended SDR family.<br />
<br />
[[Image:2qq5align2.png|framed|'''Figure 2'''<BR>Clustal Alignment of the N-terminus region of the target protein|none]]<BR><br />
<br />
==Results/structure==<br />
[[Image:pretty.png|framed|'''Figure 2'''<BR>Cartoon of a single DHRS1 unit with different structural features highlighted in different colours. |none]]<BR><br />
<br />
A single monomeric unit of DHRS1 contains 13 α helices 1 central β-sheet region consisting of 7 strands. It is thought to exist biologically as a dimer.<br />
<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
The SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised by a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P). It is part of a larger motif [S-x(12)-Y-x(3)-K] that includes two other residues involved in binding NAD(P) (Wu Q, et al 2001).<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein (Wu Q, et al 2001). It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. <br />
<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 3'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with 3-Oxoacyl-(Acyl-Carrier-protien)reductase (green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Comparison of DHRS1 to 3-Oxoacyl-(Acyl-Carrier-protien)reductase its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 0.7-3 Angstroms (fig 3).<br />
<br />
[[Image:alighn 2uved catalytic site.png|framed|'''Figure 4'''<BR>Close in view of the catalytic triad (S-Y-K)from the alignment 2uvd and DHRS1. Showing the difference in the positions of the key residues. |none]]<BR><br />
<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8221DHRS1 Results2008-06-03T06:50:00Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
<br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria. Blue branches show organisms of the anamalia kingdom, Black branches show organisms of the bacteria kingdom.<br />
<br />
Aedes aegypti and Schistosoma japonicum are both found in the anamalia kingdom, although are seperated on the graph. Both of these organisms are parasitic by nature.<br />
Aedes aegypti is commonly known as the yellow fever mosquito. Schistosoma japonicum is a parasite and one of the major infectious agents of schistosomiasis.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Clustal Alignment==<br />
<br />
Clustal alignment shows that Homo_sapiens_SDR_family_1 (an exact match for our target protein) with regards to <br />
protein sequence, contains all eight key residues (locations 117 - 121, 195,209 and 213). It also contains a <br />
sequence K-[A,S]-F-W-E-x-P-A-S at location 138 - 146 which is conserved only between land based animals.<br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
==Results/structure==<br />
[[Image:pretty.png|framed|'''Figure 2'''<BR>Cartoon of a single DHRS1 unit with different structural features highlighted in different colours. |none]]<BR><br />
<br />
A single monomeric unit of DHRS1 contains 13 α helices 1 central β-sheet region consisting of 7 strands. It is thought to exist biologically as a dimer.<br />
<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
The SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised by a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P). It is part of a larger motif [S-x(12)-Y-x(3)-K] that includes two other residues involved in binding NAD(P) (Wu Q, et al 2001).<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein (Wu Q, et al 2001). It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. <br />
<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 3'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with 3-Oxoacyl-(Acyl-Carrier-protien)reductase (green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Comparison of DHRS1 to 3-Oxoacyl-(Acyl-Carrier-protien)reductase its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 0.7-3 Angstroms (fig 3).<br />
<br />
[[Image:alighn 2uved catalytic site.png|framed|'''Figure 4'''<BR>Close in view of the catalytic triad (S-Y-K)from the alignment 2uvd and DHRS1. Showing the difference in the positions of the key residues. |none]]<BR><br />
<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8204DHRS1 Results2008-06-03T06:26:23Z<p>Antonlord: /* Results/Evolution */</p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria. Blue branches show organisms of the anamalia kingdom, Black branches show organisms of the bacteria kingdom.<br />
<br />
Aedes aegypti and Schistosoma japonicum are both found in the anamalia kingdom, although are seperated on the graph. Both of these organisms are parasitic by nature.<br />
Aedes aegypti is commonly known as the yellow fever mosquito. Schistosoma japonicum is a parasite and one of the major infectious agents of schistosomiasis.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Clustal Alignment==<br />
<br />
Clustal alignment shows that Homo_sapiens_SDR_family_1 (an exact match for our target protein) with regards to <br />
protein sequence, contains all eight key residues (locations 117 - 121, 195,209 and 213). It also contains a <br />
sequence K-[A,S]-F-W-E-x-P-A-S at location 138 - 146 which is conserved only between land based animals.<br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
==Results/structure==<br />
[[Image:pretty.png|framed|'''Figure 2'''<BR>Cartoon of a single DHRS1 unit with different structural features highlighted in different colours. |none]]<BR><br />
<br />
A single monomeric unit of DHRS1 contains 13 α helices 1 central β-sheet region consisting of 7 strands. It is thought to exist biologically as a dimer.<br />
<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
The SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised by a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P). It is part of a larger motif [S-x(12)-Y-x(3)-K] that includes two other residues involved in binding NAD(P) (Wu Q, et al 2001).<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein (Wu Q, et al 2001). It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. <br />
<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 3'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with 3-Oxoacyl-(Acyl-Carrier-protien)reductase (green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Comparison of DHRS1 to 3-Oxoacyl-(Acyl-Carrier-protien)reductase its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 0.7-3 Angstroms (fig 3).<br />
<br />
[[Image:alighn 2uved catalytic site.png|framed|'''Figure 4'''<BR>Close in view of the catalytic triad (S-Y-K)from the alignment 2uvd and DHRS1. Showing the difference in the positions of the key residues. |none]]<BR><br />
<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8139DHRS1 Results2008-06-03T05:35:55Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Clustal Alignment==<br />
<br />
Clustal alignment shows that Homo_sapiens_SDR_family_1 (an exact match for our target protein) with regards to <br />
protein sequence, contains all eight key residues (locations 117 - 121, 195,209 and 213). It also contains a <br />
sequence K-[A,S]-F-W-E-x-P-A-S at location 138 - 146 which is conserved only between land based animals.<br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
==Results/structure==<br />
<br />
DHRS1 contain 10 α helices 1 central β-sheet region.<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P). It is part of a larger motif [S-x(12)-Y-x(3)-K] that includes two other residues involved in binding NAD(P).<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein. It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. <br />
<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Comparison of DHRS1 to 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 2-3 Angstroms (fig 3)<br />
.<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8103DHRS1 Results2008-06-03T05:07:34Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
[[Image:2qq5align1.png|framed|'''Figure 1'''<BR>Clustal Alignment of target protein with blast results with marked key residues|none]]<BR><br />
<br />
==Results/structure==<br />
<br />
DHRS1 contain α helices β-sheet <br />
<br />
Comparison of DHRS1 to 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices. Key conserved residues such as the tyrosine shown are also in very similar positions eluding to a similar function.<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NAD(P). It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NAD(P).<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein. It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 2-3 Angstroms.<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=File:2qq5align2.png&diff=8057File:2qq5align2.png2008-06-03T04:38:55Z<p>Antonlord: </p>
<hr />
<div></div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=File:2qq5align1.png&diff=8056File:2qq5align1.png2008-06-03T04:38:15Z<p>Antonlord: </p>
<hr />
<div></div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8055DHRS1 Results2008-06-03T04:37:12Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
<br />
<br />
==Results/structure==<br />
<br />
Comparison of DHRS1 to 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices.<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NADPH. It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NADPH.<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein. It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 2-3 Angstroms. NADPH binding????<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8034DHRS1 Results2008-06-03T04:11:59Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria.<br />
<br />
==Results/structure==<br />
<br />
Comparison of DHRS1 to 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices.<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NADPH. It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NADPH.<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein. It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold. Importantly the key catalytic triad (S-Y-K) is still in the same place with the tips of the residues only moved 2-3 Angstroms. NADPH binding????<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Method&diff=8003DHRS1 Method2008-06-03T03:14:07Z<p>Antonlord: /* MULTIPLE SEQUENCE ALIGNMENT */</p>
<hr />
<div>==BLAST==<br />
<br />
The protein sequence for the SDR family member 1 protein being investigated was downloaded from the PDB site, using the accession code 2qq5. This was then iteratively searched in blastp using an offline, non redundant copy of the database produced on the 28th of April 2008.<br />
<br />
<br />
<br />
==MULTIPLE SEQUENCE ALIGNMENT==<br />
<br />
The results from the blast search were then screened and a selection was of these results were used for a multiple sequence alignment using ClustalX. This result was boostrapped using 1000 simulations and these values checked and more sequences were added to improve the resolution of specific branches. A bootstrapped phylogram was produced, as well as a radial tree.</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=8000DHRS1 Results2008-06-03T03:02:48Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
==Results/structure==<br />
<br />
Comparison of DHRS1 to 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices.<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NADPH. It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NADPH.<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein. It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold.<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
<br />
==Results/Evolution==<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria.<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=7999DHRS1 Results2008-06-03T03:02:20Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
==Results/structure==<br />
<br />
Comparison of DHRS1 to 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE its closest structurally related protein, finds that whilst it shares only 27% of its sequence, it is structurally very similar (Fig 2). They share many structural features including the central β-sheet region and many α helices.<br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Structure comparison==<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This puts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NADPH. It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NADPH.<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein. It forms part of the hydrophobic core most notably a strand of the β-sheet that is part of the Rossmann-fold.<br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics from DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL: DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;<br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
The phylogenic tree shows a small section of the family is contained in land based higher organisms (Bos taurus through to Mus Muluscus), a smaller section is found in sea based eukaryotes (Danio rerio and Tetraodon nigroviridis) and the majority of the family is round in bacteria. The majority of bacteria found to possess this family are proteobacteria, although there are also gram positive rod (eg. bacillus) and cyanobacteria (eg. anabena). This suggests that this particular family has been present for a long time and has evolved from bacteria, most likely proteobacteria.<br />
<br />
<br />
<br />
<br />
<br />
<BR><br />
<BR><br />
<BR><br />
[[Dehydrogenase/reductase (SDR family) member 1 | Back to Main Page]]</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Method&diff=7951DHRS1 Method2008-06-03T02:04:36Z<p>Antonlord: /* MULTIPLE SEQUENCE ALIGNMENT */</p>
<hr />
<div>==BLAST==<br />
<br />
The protein sequence for the SDR family member 1 protein being investigated was downloaded from the PDB site, using the accession code 2qq5. This was then iteratively searched in blastp using an offline, non redundant copy of the database produced on the 28th of April 2008.<br />
<br />
<br />
<br />
==MULTIPLE SEQUENCE ALIGNMENT==<br />
<br />
The results from the blast search were then screened and a selection was of these results were used for a multiple sequence alignment using ClustalX. This result was boostrapped and these values checked and more sequences were added to improve the resolution of specific branches. A bootstrapped phylogram was produced, as well as a radial tree.</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=7489DHRS1 Results2008-05-27T08:41:54Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Results/structure==<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This buts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NADPH. It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NADPH.<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein and forms part of the hydrophobic core.<br />
<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics for DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL:DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Method&diff=7488DHRS1 Method2008-05-27T08:41:33Z<p>Antonlord: </p>
<hr />
<div>==BLAST==<br />
<br />
The protein sequence for the SDR family member 1 protein being investigated was downloaded from the PDB site, using the accession code 2qq5. This was then iteratively searched in blastp using an offline, non redundant copy of the database produced on the 28th of April 2008.<br />
<br />
<br />
<br />
==MULTIPLE SEQUENCE ALIGNMENT==<br />
<br />
The results from the blast search were then screened and a selection was of these results were used for a multiple sequence alignment using ClustalX. This result was boostrapped and these values checked and more sequences were added to improve the resolution of specific branches. A bootstrapped phylogram was produces, aswell as a radial tree.</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Method&diff=7487DHRS1 Method2008-05-27T08:41:15Z<p>Antonlord: </p>
<hr />
<div>==BLAST==<br />
<br />
The protein sequence for the SDR family member 1 protein being investigated was downloaded from the PDB site, using the accession code 2qq5. This was then iteratively searched in blastp using an offline, non redundant copy of the database produced on the 28th of April 2008.<br />
<br />
<br />
<br />
==MULTIPLE SEQUENCE ALIGNMENT==<br />
<br />
The results from the blast search were then screened and a selection was of these results were used for a multiple sequence alignment using ClustalX. This result was boostrapped and these values checked and more sequences were added to improve the resolution of specific branches. A bootstrapped phylogram was produces, aswell as a radial tree.<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR></div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=7486DHRS1 Results2008-05-27T08:41:00Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
==Results/structure==<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This buts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NADPH. It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NADPH.<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein and forms part of the hydrophobic core.<br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics for DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL:DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Results&diff=7478DHRS1 Results2008-05-27T08:29:15Z<p>Antonlord: </p>
<hr />
<div>[[Image:PBB GE DHRS1 213279 at fs.png|framed|'''Figure 1'''<BR>DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008|none]]<BR><br />
<br />
[[Image:align 2uvd.png|framed|'''Figure 2'''<BR>Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well. |none]]<BR><br />
<br />
Results/structure<br />
Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.<br />
<br />
SDR family is part of the Super Family; NAD(P)-binding Rossmann-fold domain proteins all of which have the Rossmann-fold domain, which is characterised a central β-sheet surrounded by α-helicies. This buts them in the Alpha and Beta proteins (α/β) class.<br />
<br />
Some key residues are conserved across the entire family. Notable a Tyrosine that binds NADPH. It is part of a larger motif (SxxxxxxxxxxxxYxxxK) that includes two other residues involved in binding NADPH.<br />
<br />
There is another highly conserved motif (LDVLD) involved in the initial folding of the protein and forms part of the hydrophobic core.<br />
<br />
==BLAST==<br />
<br />
The protein sequence for the SDR family member 1 protein being investigated was downloaded from the PDB site, using the accession code 2qq5. This was then iteratively searched in blastp using an offline, non redundant copy of the database produced on the 28th of April 2008.<br />
<br />
<br />
<br />
==MULTIPLE SEQUENCE ALIGNMENT==<br />
<br />
The results from the blast search were then screened and a selection was of these results were used for a multiple sequence alignment using ClustalX. This result was boostrapped and these values checked and more sequences were added to improve the resolution of specific branches. A bootstrapped phylogram was produces, aswell as a radial tree.<br />
[[Image:StrappedTree.png|1050px|'''Figure 3'''<BR>Phylogenetic Tree of SDR Family with Bootstrapping values|none]]<BR><br />
<br />
[[Image:StrappedTree2qq5.PNG|1050px|'''Figure 4'''<BR>Unrooted phylogram for Dehydrogenase/reductase (SDR family)|none]]<BR><br />
<br />
===Table 1===<br />
'''PDB/chain identifiers and structural alignment statistics for DALI search'''<br />
No: Chain Z rmsd lali nres %id Description<br />
1: 2qq5-A 48.1 0.0 238 238 100 MOL:DEHYDROGENASE/REDUCTASE SDR1;<br />
2: 2uvd-A 29.6 2.1 220 246 27 MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN) REDUCTASE; <br />
3: 1yde-F 29.3 2.1 216 256 29 MOL: RETINAL DEHYDROGENASE/REDUCTASE 3; <br />
4: 1vl8-B 29.1 2.0 220 252 27 MOL: GLUCONATE 5-DEHYDROGENASE; <br />
5: 2bgk-A 29.0 2.1 219 267 25 MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; <br />
6: 2q2q-D 28.9 2.0 217 255 26 MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE; <br />
7: 1rwb-F 28.8 2.2 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
8: 1rwb-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
9: 1gee-A 28.8 2.3 222 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
10: 1gco-A 28.8 2.3 222 261 24 MOL: GLUCOSE DEHYDROGENASE; <br />
11: 2zat-A 28.7 2.1 221 251 23 MOL: DEHYDROGENASE/REDUCTASE SDR4;<br />
12: 1gee-B 28.7 2.3 221 261 24 MOL: GLUCOSE 1-DEHYDROGENASE; <br />
13: 1gco-E 28.7 2.3 221 261 24 MOL: GLUCOSE DEHYDROGENASE;</div>Antonlordhttp://compbio.biosci.uq.edu.au/mediawiki/index.php?title=DHRS1_Introduction&diff=7457DHRS1 Introduction2008-05-27T07:58:44Z<p>Antonlord: /* Introduction to DHRS1 */</p>
<hr />
<div>==Introduction to DHRS1==<br />
<br />
Short-chain Dehydrogenase/Reductase (SDR) is a large protein family currently numbering about 2000 members [http://www.proteinscience.org/cgi/content/full/11/3/636 (Kallberg et al. 2002)]. It also goes by the alternative name of the tyrosine-dependent oxidoreductase protein family [http://www.biomedcentral.com/1471-2091/3/19 (Edgar. 2002)] because of their conserved tyrosine residue at position 152. The SDR family is defined by a rossman fold, and highly conserved Ser, Tyr and Lys residues[http://www.proteinscience.org/cgi/content/full/11/3/636 (Kallberg et al 2001)]. SDR proteins have a length of about 250 amino acids (aa) and show approximately 15-30% sequence similarity/identity. This is relatively low when compared to other families. Despite this, members still have large degree of structural similarity, and it has therefore been suggested that the structure of dehydrogenases has arisen through gene fusion of a common ancestral coenzyme nucleotide sequence with various substrate specific domains [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=6789320 (Benyajati et al. 1981)].<br />
<br />
Dehydrogenase/Reductase member 1 (DHRS1) is one member of the SDR family found in chromosome 14 in Homo sapiens. The role of a dehydrogenase is to oxidize substrates, that is the removal of electrons (Refer to Figure 1) [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1066084 (Takahoma, 1983)]. The acceptor is generally a NAD+/NADP. NAD (Nicotinamide adenine dinucleotide is found in all living cells. The role of NAD+ in cells is to carry electrons from one reaction to another. Reductase enzymes lower activation energy in reduction reactions. Reduction reactions involve the gain of electrons (Refer to Figure 1). Activation energy is the amount of energy needed to be overcome in order for a chemical reaction to occur.<br />
<BR><BR><br />
[[Image:Redox Halves.png|400px|Redox Reactions]]<BR><br />
<BR><br />
Currently the exact function of DHRS1 is unpublished. The objective of this project is to find relative functional, structural and evolutional information on DHRS1 in order to make an appropriate conclusion on its role organism function. <br />
<BR></div>Antonlord