EzCatDB: S00326
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DB codeS00326
RLCP classification9.1050.440000.8010 : Hydride transfer
9.5010.536200.8010 : Hydride transfer
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
E.C.1.1.1.53

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,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

P19992
Protein name3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase3alpha(or 20beta)-hydroxysteroid dehydrogenase
cortisone reductase
(R)-20-hydroxysteroid dehydrogenase
dehydrogenase, 20beta-hydroxy steroid
Delta4-3-ketosteroid hydrogenase
20beta-hydroxysteroid dehydrogenase
3alpha,20beta-hydroxysteroid:NAD+-oxidoreductase
NADH-20beta-hydroxysteroid dehydrogenase
20beta-HSD
SynonymsEC 1.1.1.53
PfamPF00106 (adh_short)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00120Bile acid biosynthesis
MAP00140C21-Steroid hormone metabolism

UniProtKB:Accession NumberP19992
Entry nameHSD_STREX
ActivityAndrostan-3-alpha,17-beta-diol + NAD(+) = 17-beta-hydroxyandrostan-3-one + NADH.
SubunitHomotetramer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00003C03852C00004C03917C00080
CompoundNAD+Androstan-3alpha,17beta-diolNADH17beta-Hydroxyandrostan-3-oneH+
Typeamide group,amine group,nucleotidecarbohydrate,steroidamide group,amine group,nucleotidecarbohydrate,steroidothers
ChEBI15846
36713
16908
16330
15378
PubChem5893
15818
440143
439153
10635
1038
             
1hdcAUnboundUnboundUnboundAnalogue:CBO 
1hdcBUnboundUnboundUnboundAnalogue:CBO 
1hdcCUnboundUnboundUnboundAnalogue:CBO 
1hdcDUnboundUnboundUnboundAnalogue:CBO 
2hsdABound:NADUnboundUnboundUnbound 
2hsdBBound:NADUnboundUnboundUnbound 
2hsdCBound:NADUnboundUnboundUnbound 
2hsdDBound:NADUnboundUnboundUnbound 

Active-site residues
resource
Swiss-prot;P19992 & literature [13]
pdbCatalytic residues
         
1hdcASER 139;TYR 152;LYS 156
1hdcBSER 139;TYR 152;LYS 156
1hdcCSER 139;TYR 152;LYS 156
1hdcDSER 139;TYR 152;LYS 156
2hsdASER 139;TYR 152;LYS 156
2hsdBSER 139;TYR 152;LYS 156
2hsdCSER 139;TYR 152;LYS 156
2hsdDSER 139;TYR 152;LYS 156

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[12]

[13]Fig.8b, p.632-637
[15]Fig.3

references
[1]
PubMed ID168869
JournalBiochem J
Year1975
Volume145
Pages483-9
AuthorsGibb W, Jeffery J
TitleThe altered specificity of cortisone reductase with certain retroandrostan-3-one substrates.
[2]
PubMed ID172381
JournalBiochem Soc Trans
Year1975
Volume3
Pages674-5
AuthorsWhite IH, Jeffery J
TitleThe functioning of a nicotinamide--adenine dinucleotide-dependent dehydrogenase and the structure adjacent to the reacting carbon atom of the substrate.
[3]
PubMed ID902901
JournalBiochem Soc Trans
Year1977
Volume5
Pages723-4
AuthorsWhite IH, Jeffery J
TitleCortisone reductase and some small non-steroid analogues of its steroid substrates.
[4]
PubMed ID6938245
JournalBiochim Biophys Acta
Year1980
Volume616
Pages143-52
AuthorsPasta P, Carrea G, Longhi R, Antonini E
TitleRenaturation and urea-induced denaturation of 20 beta-hydroxysteroid dehydrogenase studied in solution and in the immobilized state.
[5]
PubMed ID6930328
JournalChem Pharm Bull (Tokyo)
Year1980
Volume28
Pages730-6
AuthorsHayakawa T, Tanimoto T, Kawamura J
TitleStructural requirements in 20-oxo-steroids for interaction with the catalytic site of 20 beta-hydroxysteroid dehydrogenase.
[6]
PubMed ID6929616
JournalSteroids
Year1980
Volume35
Pages111-8
AuthorsSweet F, Ahmed R, Morgan TE, Sweet BC
TitleBifunctional enzyme activity at the same active site: competitive inhibition kinetics with 3 alpha/20 beta-hydroxysteroid dehydrogenase.
[7]
PubMed ID6944159
JournalChem Pharm Bull (Tokyo)
Year1981
Volume29
Pages476-84
AuthorsKawamura J, Tanimoto T, Fukuda H, Hayakawa T
TitleStructural requirements in 20-oxo-steroids for interaction with the binding site of 20beta-hydroxysteroid dehydrogenase.
[8]
PubMed ID6587118
JournalJ Mol Biol
Year1984
Volume175
Pages225-7
AuthorsFitzgerald PM, Duax WL, Punzi JS, Orr JC
TitleCrystallization and preliminary crystallographic study of 3 alpha, 20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans.
[9]
PubMed ID3455925
JournalJ Biol Chem
Year1986
Volume261
Pages1306-8
AuthorsGhosh D, Punzi JS, Duax WL
TitleCrystals of active tetramers of 3 alpha, 20 beta-hydroxysteroid dehydrogenase.
[10]
PubMed ID2064995
JournalJ Steroid Biochem Mol Biol
Year1991
Volume38
Pages787-94
AuthorsOhno S, Nakajin S, Shinoda M
Title20 beta-hydroxysteroid dehydrogenase of neonatal pig testis: 3 alpha/beta-hydroxysteroid dehydrogenase activities catalyzed by highly purified enzyme.
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)
Medline ID92052211
PubMed ID1946424
JournalProc Natl Acad Sci U S A
Year1991
Volume88
Pages10064-8
AuthorsGhosh D, Weeks CM, Grochulski P, Duax WL, Erman M, Rimsay RL, Orr JC
TitleThree-dimensional structure of holo 3 alpha,20 beta-hydroxysteroid dehydrogenase: a member of a short-chain dehydrogenase family.
Related UniProtKBP19992
[12]
CommentsX-ray crystallography
PubMed ID7866748
JournalStructure
Year1994
Volume2
Pages973-80
AuthorsGhosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W
TitleMechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor.
Related PDB1hdc
[13]
CommentsX-ray crystallography
PubMed ID7922040
JournalStructure
Year1994
Volume2
Pages629-40
AuthorsGhosh D, Wawrzak Z, Weeks CM, Duax WL, Erman M
TitleThe refined three-dimensional structure of 3 alpha,20 beta-hydroxysteroid dehydrogenase and possible roles of the residues conserved in short-chain dehydrogenases.
Related PDB2hsd
[14]
PubMed ID7696141
JournalJ Steroid Biochem Mol Biol
Year1995
Volume52
Pages209-18
AuthorsBuczko E, Koh YC, Miyagawa Y, Dufau ML
TitleThe rat 17 alpha-hydroxylase-17,20-desmolase (CYP17) active site: computerized homology modeling and site directed mutagenesis.
[15]
PubMed ID9029722
JournalSteroids
Year1997
Volume62
Pages95-100
AuthorsDuax WL, Ghosh D
TitleStructure and function of steroid dehydrogenases involved in hypertension, fertility, and cancer.

comments
This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, along with Drosophia alcohol dehydrogenase (S00319 in EzCatDB). This enzyme has got a catalytic triad composed of conserved residues, Ser, Tyr, and Lys. The conformation of these residues, compared to that of the NAD molecule, seems to be similar to that of the homologous enzymes. Thus, the catalytic site seems to catalyze the following reversible reactions.
(A) Hydride transfer from substrate to NAD (Dehydrogenation):
(A0) Lys156 modulates the activity (or pKa) of Tyr152 via 2'-hydroxyl group of NAD, along with the N1 atom of the nicotinamide group in NAD, whereas Ser139 modulates the pKa of hydroxyl oxygen of the substrate.
(A1) Tyr152 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 NADH to substrate (Reduction):
(B0) Lys156 modulates the activity (or pKa) of Tyr152 via 2'-hydroxyl group of NAD(P)H, along with the N1 atom of the nicotinamide group in NADH, whereas Ser139 modulates the pKa of carbonyl oxygen of the substrate.
(B1) Tyr152 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.

createdupdated
2004-07-132011-06-21
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