DB code: S00610

RLCP classification 9.5010.536200.8010 : Hydride transfer
9.1050.440000.8010 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.1.1.51
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00625 S00319 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P19871 3-beta-hydroxysteroid dehydrogenase
EC 1.1.1.51
PF00106 (adh_short)
[Graphical View]

KEGG enzyme name
3(or 17)beta-Hydroxysteroid dehydrogenase
beta-Hydroxy steroid dehydrogenase
17-Ketoeductase
17beta-Hydroxy steroid dehydrogenase
3beta-Hydroxysteroid dehydrogenase
17beta-Hydroxy steroid dehydrogenase
3beta-Hydroxy steroid dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P19871 3BHD_COMTE Testosterone + NAD(P)(+) = androst-4-ene-3,17-dione + NAD(P)H. Homotetramer.

KEGG Pathways
Map code Pathways E.C.
MAP00150 Androgen and estrogen metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00535 C00003 C00006 C00280 C00004 C00005 C00080
E.C.
Compound testosterone NAD+ NADP+ androst-4-ene-3,17-dione NADH NADPH H+
Type carbohydrate,steroid amide group,amine group,nucleotide amide group,amine group,nucleotide carbohydrate,steroid amide group,amine group,nucleotide amide group,amine group,nucleotide others
ChEBI 17347
15846
18009
16422
16908
16474
15378
PubChem 6013
5893
5886
6128
439153
5884
1038
1hxhA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1hxhB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1hxhC00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1hxhD00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1hxhA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1hxhB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1hxhC00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1hxhD00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Fig.1, p.86
[2]
Fig.4, p.38
[3]
Fig.9, Fig.12, Fig.13, p.134-139
[4]
Fig.5, p.14666-14667
[5]
Fig.4, Fig.5, p.25680-25682

References
[1]
Resource
Comments
Medline ID
PubMed ID 2991019
Journal FEBS Lett
Year 1985
Volume 188
Pages 85-90
Authors Minard P, Legoy MD, Thomas D
Title 3 beta, 17 beta-hydroxysteroid dehydrogenase of Pseudomonas testosteroni. Kinetic evidence for the bifunctional activity at a common catalytic site.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8993315
Journal Biochemistry
Year 1997
Volume 36
Pages 34-40
Authors Oppermann UC, Filling C, Berndt KD, Persson B, Benach J, Ladenstein R, Jornvall H
Title Active site directed mutagenesis of 3 beta/17 beta-hydroxysteroid dehydrogenase establishes differential effects on short-chain dehydrogenase/reductase reactions.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 10668397
Journal Vitam Horm
Year 2000
Volume 58
Pages 121-48
Authors Duax WL, Ghosh D, Pletnev V
Title Steroid dehydrogenase structures, mechanism of action, and disease.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12475215
Journal Biochemistry
Year 2002
Volume 41
Pages 14659-68
Authors Benach J, Filling C, Oppermann UC, Roversi P, Bricogne G, Berndt KD, Jornvall H, Ladenstein R
Title Structure of bacterial 3beta/17beta-hydroxysteroid dehydrogenase at 1.2 A resolution: a model for multiple steroid recognition.
Related PDB 1hxh
Related UniProtKB P19871
[5]
Resource
Comments
Medline ID
PubMed ID 11976334
Journal J Biol Chem
Year 2002
Volume 277
Pages 25677-84
Authors Filling C, Berndt KD, Benach J, Knapp S, Prozorovski T, Nordling E, Ladenstein R, Jornvall H, Oppermann U
Title Critical residues for structure and catalysis in short-chain dehydrogenases/reductases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12604210
Journal Chem Biol Interact
Year 2003
Volume 143-144
Pages 247-53
Authors Oppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, Shafqat J, Nordling E, Kallberg Y, Persson B, Jornvall H
Title Short-chain dehydrogenases/reductases (SDR): the 2002 update.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the short-chain dehydrogenases/reductases(SDR) family.
This enzyme catalyzes both the dehydrogenation (oxidation) and reduction of the beta-hydroxyl groups at position-3 and -17 of steroid compounds (see [4]).
Thus, this enzyme catalyzes the following reactions, according to the literature [2], [4] and [5]:
(A) Hydride transfer from substrate to NAD(P) (Dehydrogenation):
(A0) Lys155 modulates the activity (or pKa) of Tyr151 via 2'-hydroxyl group of NAD(P), along with the N1 atom of the nicotinamide group in NAD(P), whereas Ser138 modulates the pKa of hydroxyl oxygen of the substrate.
(A1) Tyr151 acts as a general base to deprotonate the hydroxyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the carbon atom with the hydroxyl group of the substrate to the C4 atom of the nicotinamide.
(B) Hydride transfer from NAD(P)H to substrate (Reduction):
(B0) Lys155 modulates the activity (or pKa) of Tyr151 via 2'-hydroxyl group of NAD(P)H, along with the N1 atom of the nicotinamide group in NAD(P)H, whereas Ser138 modulates the pKa of carbonyl oxygen of the substrate.
(B1) Tyr151 acts as a general acid to protonate the carbonyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4 atom of the nicotinamide to the carbonyl carbon of the substrate.
###
According to the literature [5] and [6], the mainchain carbonyl group of Asn111, which is conserved in the superfamily, seems to be involved in proton relay system, by interacting with a water that is also bound to Lys155. However, currently the Asn residue has not been included in the catalytic site in this entry.

Created Updated
2009-01-15 2011-06-17