EzCatDB: S00610
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DB codeS00610
RLCP classification9.1050.440000.8010 : Hydride transfer
9.5010.536200.8010 : Hydride transfer
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
E.C.1.1.1.51

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00543,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

Enzyme Name
UniProtKBKEGG

P19871
Protein name3-beta-hydroxysteroid dehydrogenase3(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
SynonymsEC 1.1.1.51
PfamPF00106 (adh_short)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00150Androgen and estrogen metabolism

UniProtKB:Accession NumberP19871
Entry name3BHD_COMTE
ActivityTestosterone + NAD(P)(+) = androst-4-ene-3,17-dione + NAD(P)H.
SubunitHomotetramer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00535C00003C00006C00280C00004C00005C00080
CompoundtestosteroneNAD+NADP+androst-4-ene-3,17-dioneNADHNADPHH+
Typecarbohydrate,steroidamide group,amine group,nucleotideamide group,amine group,nucleotidecarbohydrate,steroidamide group,amine group,nucleotideamide group,amine group,nucleotideothers
ChEBI17347
15846
18009
16422
16908
16474
15378
PubChem6013
5893
5886
6128
439153
5884
1038
               
1hxhA00UnboundUnboundUnboundUnboundUnboundUnbound 
1hxhB00UnboundUnboundUnboundUnboundUnboundUnbound 
1hxhC00UnboundUnboundUnboundUnboundUnboundUnbound 
1hxhD00UnboundUnboundUnboundUnboundUnboundUnbound 

Active-site residues
resource
literature [2], [4]
pdbCatalytic residues
         
1hxhA00SER 138;TYR 151;LYS 155
1hxhB00SER 138;TYR 151;LYS 155
1hxhC00SER 138;TYR 151;LYS 155
1hxhD00SER 138;TYR 151;LYS 155

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID2991019
JournalFEBS Lett
Year1985
Volume188
Pages85-90
AuthorsMinard P, Legoy MD, Thomas D
Title3 beta, 17 beta-hydroxysteroid dehydrogenase of Pseudomonas testosteroni. Kinetic evidence for the bifunctional activity at a common catalytic site.
[2]
PubMed ID8993315
JournalBiochemistry
Year1997
Volume36
Pages34-40
AuthorsOppermann UC, Filling C, Berndt KD, Persson B, Benach J, Ladenstein R, Jornvall H
TitleActive site directed mutagenesis of 3 beta/17 beta-hydroxysteroid dehydrogenase establishes differential effects on short-chain dehydrogenase/reductase reactions.
[3]
PubMed ID10668397
JournalVitam Horm
Year2000
Volume58
Pages121-48
AuthorsDuax WL, Ghosh D, Pletnev V
TitleSteroid dehydrogenase structures, mechanism of action, and disease.
[4]
PubMed ID12475215
JournalBiochemistry
Year2002
Volume41
Pages14659-68
AuthorsBenach J, Filling C, Oppermann UC, Roversi P, Bricogne G, Berndt KD, Jornvall H, Ladenstein R
TitleStructure of bacterial 3beta/17beta-hydroxysteroid dehydrogenase at 1.2 A resolution: a model for multiple steroid recognition.
Related PDB1hxh
Related UniProtKBP19871
[5]
PubMed ID11976334
JournalJ Biol Chem
Year2002
Volume277
Pages25677-84
AuthorsFilling C, Berndt KD, Benach J, Knapp S, Prozorovski T, Nordling E, Ladenstein R, Jornvall H, Oppermann U
TitleCritical residues for structure and catalysis in short-chain dehydrogenases/reductases.
[6]
PubMed ID12604210
JournalChem Biol Interact
Year2003
Volume143-144
Pages247-53
AuthorsOppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, Shafqat J, Nordling E, Kallberg Y, Persson B, Jornvall H
TitleShort-chain dehydrogenases/reductases (SDR): the 2002 update.

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.

createdupdated
2009-01-152011-06-17


Copyright: Nozomi Nagano, JST & CBRC-AIST
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