DHRS1 Results

Figure 1
DHRS1 Gene expression pattern. Reproduced from Genomics Institute of Novartis Research Foundation. 2008

Results/structure

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.

Figure 2
Cartoon of DHRS1 (cyan/magenta) aligned with Oxoacyl-(Acyl-Carrier-protien)(green/red) the key catalytic Tyrosine residue is shown in as well.

Structure comparison

Dehydrogenase/reductase SDR family member 1 has highly conserved structure compared across the SDR family.

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.

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.

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.

Table 1

PDB/chain identifiers and structural alignment statistics from DALI search

No:	Chain	Z	rmsd	lali	nres	%id	Description
1:	2qq5-A	48.1	0.0	238	238	100	MOL: DEHYDROGENASE/REDUCTASE SDR1;
2:	2uvd-A	29.6	2.1	220	246	27	MOL: 3-OXOACYL-(ACYL-CARRIER-PROTEIN)  REDUCTASE;             
3:	1yde-F	29.3	2.1	216	256	29	MOL: RETINAL DEHYDROGENASE/REDUCTASE 3;                         
4:	1vl8-B	29.1	2.0	220	252	27	MOL: GLUCONATE 5-DEHYDROGENASE;                                 
5:	2bgk-A	29.0	2.1	219	267	25	MOL: RHIZOME SECOISOLARICIRESINOL DEHYDROGENASE; 
6:	2q2q-D	28.9	2.0	217	255	26	MOL: BETA-D-HYDROXYBUTYRATEDEHYDROGENASE;                                
7:	1rwb-F	28.8	2.2	221	261	24	MOL: GLUCOSE 1-DEHYDROGENASE;                                   
8:	1rwb-A	28.8	2.3	222	261	24	MOL: GLUCOSE 1-DEHYDROGENASE;                                   
9:	1gee-A	28.8	2.3	222	261	24	MOL: GLUCOSE 1-DEHYDROGENASE;                                   
10:	1gco-A	28.8	2.3	222	261	24	MOL: GLUCOSE DEHYDROGENASE;                                     
11:	2zat-A	28.7	2.1	221	251	23	MOL: DEHYDROGENASE/REDUCTASE SDR4;
12:	1gee-B	28.7	2.3	221	261	24	MOL: GLUCOSE 1-DEHYDROGENASE;                                   
13:	1gco-E	28.7	2.3	221	261	24	MOL: GLUCOSE DEHYDROGENASE;

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