3b5q Function: Difference between revisions

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Sulfatases are enzymes,which hydrolyse sulfate ester bonds of substrates. These are categorised as '''EC 3.1.6.''' in enzyme classifications. Most of the family members has shown to contain a highly conserved cystine residue and a bivalent metal binding site.
Sulfatases are enzymes,which hydrolyse sulfate ester bonds of substrates. These are categorised as '''EC 3.1.6.''' in enzyme classifications. Most of the family members has shown to contain a highly conserved cystine residue and a bivalent metal binding site.


Arylsulphatase A (ASA) is a lysosomal enzyme which hydrolyzes cerebroside sulphate. Arylsulphatase B (ASB) hydrolyzes the sulphate ester group from N-acetylgalactosamine 4-sulphate group of dermatan sulphate.
Arylsulphatase A (ASA) is a lysosomal enzyme which hydrolyzes cerebroside sulphate. Arylsulphatase B (ASB)( Also a lysosomal enzyme)  hydrolyzes the sulphate ester group from N-acetylgalactosamine 4-sulphate group of dermatan sulphate.




  arylsulphatase C (ASD) and E (ASE); steryl-sulphatase (STS), a membrane bound microsomal enzyme which hydrolyzes 3-beta-hydroxy steroid sulphates; iduronate 2-sulphatase precursor (IDS), a lysosomal enzyme that hydrolyzes the 2-sulphate groups from non-reducing-terminal iduronic acid residues in dermatan sulphate and heparan sulphate; N-acetylgalactosamine-6-sulphatase , which hydrolyzes the 6-sulphate groups of the N-acetyl-d-galactosamine 6-sulphate units of chondroitin sulphate and the D-galactose 6-sulphate units of keratan sulphate; glucosamine-6-sulphatase (G6S), which hydrolyzes the N-acetyl-D-glucosamine 6-sulphate units of heparan sulphate and keratan sulphate; N-sulphoglucosamine sulphohydrolase (sulphamidase), the lysosomal enzyme that catalyzes the hydrolysis of N-sulpho-d-glucosamine into glucosamine and sulphate; sea urchin embryo arylsulphatase ; green algae arylsulphatase , which plays an important role in the mineralization of sulphates; and arylsulphatase from Escherichia coli (aslA), Klebsiella aerogenes (gene atsA) and Pseudomonas aeruginosa (gene atsA).
  Arylsulphatase C (ASD), E (ASE) and steryl-sulphatase (STS)
a membrane bound microsomal enzyme which hydrolyzes 3-beta-hydroxy steroid sulphates; iduronate 2-sulphatase precursor (IDS), a lysosomal enzyme that hydrolyzes the 2-sulphate groups from non-reducing-terminal iduronic acid residues in dermatan sulphate and heparan sulphate; N-acetylgalactosamine-6-sulphatase , which hydrolyzes the 6-sulphate groups of the N-acetyl-d-galactosamine 6-sulphate units of chondroitin sulphate and the D-galactose 6-sulphate units of keratan sulphate; glucosamine-6-sulphatase (G6S), which hydrolyzes the N-acetyl-D-glucosamine 6-sulphate units of heparan sulphate and keratan sulphate; N-sulphoglucosamine sulphohydrolase (sulphamidase), the lysosomal enzyme that catalyzes the hydrolysis of N-sulpho-d-glucosamine into glucosamine and sulphate; sea urchin embryo arylsulphatase ; green algae arylsulphatase , which plays an important role in the mineralization of sulphates; and arylsulphatase from Escherichia coli (aslA), Klebsiella aerogenes (gene atsA) and Pseudomonas aeruginosa (gene atsA).
Clan
Clan



Revision as of 02:49, 27 May 2008

Protein data base profile characteris arylsulfatase asa hydrolase and a sulfatase. A hydrolase is an enzyme which hydrolyses a chemical bond. The general reaction can be shown as follows.

Hydrolase.png


Hydrolases are named as EC 3 in enzyme classification.




Function of sulfatases

Sulfatases are enzymes,which hydrolyse sulfate ester bonds of substrates. These are categorised as EC 3.1.6. in enzyme classifications. Most of the family members has shown to contain a highly conserved cystine residue and a bivalent metal binding site.

Arylsulphatase A (ASA) is a lysosomal enzyme which hydrolyzes cerebroside sulphate. Arylsulphatase B (ASB)( Also a lysosomal enzyme) hydrolyzes the sulphate ester group from N-acetylgalactosamine 4-sulphate group of dermatan sulphate.


Arylsulphatase C (ASD), E (ASE) and steryl-sulphatase (STS)
a membrane bound microsomal enzyme which hydrolyzes 3-beta-hydroxy steroid sulphates; iduronate 2-sulphatase precursor (IDS), a lysosomal enzyme that hydrolyzes the 2-sulphate groups from non-reducing-terminal iduronic acid residues in dermatan sulphate and heparan sulphate; N-acetylgalactosamine-6-sulphatase , which hydrolyzes the 6-sulphate groups of the N-acetyl-d-galactosamine 6-sulphate units of chondroitin sulphate and the D-galactose 6-sulphate units of keratan sulphate; glucosamine-6-sulphatase (G6S), which hydrolyzes the N-acetyl-D-glucosamine 6-sulphate units of heparan sulphate and keratan sulphate; N-sulphoglucosamine sulphohydrolase (sulphamidase), the lysosomal enzyme that catalyzes the hydrolysis of N-sulpho-d-glucosamine into glucosamine and sulphate; sea urchin embryo arylsulphatase ; green algae arylsulphatase , which plays an important role in the mineralization of sulphates; and arylsulphatase from Escherichia coli (aslA), Klebsiella aerogenes (gene atsA) and Pseudomonas aeruginosa (gene atsA).

Clan

Functional site

MSA data revealed some conserved residues on the sequence. They were mapped on the three dimantional structure.

Zn Cl n pocket.png


Highly conserved regions of the protein revealed in MSA are highlighted in blue, while ligands; Zn and Cl; are shown in green and grey respectively. However region of high conservation seems to be physically further from ligand binding sites. May be sudgessting that ligands only play a role in stabilizing the protein conformation, hense the active site; for the enzyme to perfprm its catalytic functions.


Zn Cl surface.png

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Arylsulfatase K (BT1596) Interactions with other proteins

Net.png


Input Protein

  • BT1596 Putative sulfatase yidJ (481 aa) of Bacteroides thetaiotaomicron.

Predicted Functional Partners

  • BT3796: Putative secreted sulfatase ydeN (518 aa).
  • BT1595 Transcription termination factor rho (722 aa).
  • BT1597 Two-component system sensor histidine kinase (539 aa).
  • BT3057 N-acetylgalactosamine-6-sulfatase (508 aa).
  • BT1598 Putative two-component system sensor histidine (655 aa).
  • BT3101 N-sulphoglucosamine sulphohydrolase (455 aa).
  • BT3489 Arylsulfatase B {UniProtKB/TrEMBL-Q8A219} (458 aa).



N-acetylgalactosamine-6-sulfatase cleaves the 6-sulfate groups of N-acetyl-D-galactosamine 6-sulfate units in chondroitin sulfate and D-galactose 6-sulfate units in keratan sulfate.N-sulphoglucosamine sulphohydrolase is also known as heparine sulfamidase, which catalyses the hydrolysis of Sulfur-Nitrogen bonds. N-sulphoglucosamine sulphohydrolase is rsponsible for the degradation of glucosaminlglycan and glycan structure of extra cellular matrix.

N-sulfo-D-glucosamine + H(2)O <=> D-glucosamine + sulfate

Structural alignment

  • Three dimentional structure of arylsulfatase was aligned with other available structures using DALI server (structural alignment). Resuls are shown in 'figure 4'.
 No:  Chain   Z    rmsd lali nres  %id   Description
  1:  3b5q-A 73.6  0.0  464   464  100   MOLECULE: PUTATIVE SULFATASE YIDJ;                                   
  2:  3b5q-B 70.2  0.3  464   467  100   MOLECULE: PUTATIVE SULFATASE YIDJ;                                   
  3:  2qzu-A 35.1  2.5  375   465   25   MOLECULE: PUTATIVE SULFATASE YIDJ;                                   
  4:  1fsu   28.7  2.8  344   474   22   MOLECULE: N-ACETYLGALACTOSAMINE-4-SULFATASE;                         
  5:  1n2l-A 28.4  3.0  343   483   25   MOLECULE: ARYLSULFATASE A;                                           
  6:  1n2k-A 28.3  3.2  344   482   25   MOLECULE: ARYLSULFATASE A;                                           
  7:  1e3c-P 28.2  3.2  344   481   26   MOLECULE: ARYLSULFATASE A;                                           
  8:  1e33-P 28.2  3.1  344   480   25   MOLECULE: ARYLSULFATASE A;                                           
  9:  1e2s-P 28.2  3.1  343   481   25   MOLECULE: ARYLSULFATASE A;                                           
 10:  1e1z-P 28.1  3.2  344   481   26   MOLECULE: ARYLSULFATASE A;                                           
 11:  1auk   27.9  3.1  343   481   25   MOLECULE: ARYLSULFATASE A;  

Figure 4: Structurally related proteins. (No 1 and 2 are two chains of arylsulfatase K).


  • The function of highly related proteins were found using ProFunc


Putative Sulfatase YIDI hydrolyses sulfuric ester bonds of its substrate hence significant in metabolism.
Arylsulfatase A has both sulfuric ester hydrolase and phosphoric monoester hydrolase activities.


Comparison of Motifs

1 Putative sulfatase yidj motifs

Bw28.jpg

2 Arylsulfatase A. Synonym: cerebroside-3-sulfate-sulfatase motifs

1auk.jpg

3 N-acetylgalactosamine-4-sulfatase motifs. (Chain: a. Synonym: arylsulfatase b, asb, 4-sulfatase)

1fsu.jpg


Motifs PF00884 and PTHR10342 are conserved among all three proteins. This is indicative of a some structural similarity in their substrates. These proteins may carry out a similar catalytic reaction or participate in slightly different aspects of a common catalytic activity. The second possibility seems to be stronger considering all three enzymes are found in tha same metabolic pathway, in close proximity to each other. All the resulted motifs are found in a sulfatase enzyme while they all belong to Alkaline phosphatase-like protein superfamily.
































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