DB code: S00326

RLCP classification	9.1050.440000.8010 : Hydride transfer
RLCP classification	9.5010.536200.8010 : Hydride transfer
CATH domain	3.40.50.720 : Rossmann fold	Catalytic domain
E.C.	1.1.1.53
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
3.40.50.720 : Rossmann fold	S00543 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

CATH domain

Related DB codes (homologues)

3.40.50.720 : Rossmann fold

S00543 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

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Pfam
P19992	3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase	EC 1.1.1.53	PF00106 (adh_short) [Graphical View]

KEGG enzyme name
3alpha(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

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P19992	HSD_STREX	Androstan-3-alpha,17-beta-diol + NAD(+) = 17-beta-hydroxyandrostan-3-one + NADH.	Homotetramer.

KEGG Pathways
Map code	Pathways	E.C.
MAP00120	Bile acid biosynthesis
MAP00140	C21-Steroid hormone metabolism

Compound table
	Substrates		Products			Intermediates
KEGG-id	C00003	C03852	C00004	C03917	C00080
E.C.
Compound	NAD+	Androstan-3alpha,17beta-diol	NADH	17beta-Hydroxyandrostan-3-one	H+
Type	amide group,amine group,nucleotide	carbohydrate,steroid	amide group,amine group,nucleotide	carbohydrate,steroid	others
ChEBI	15846 15846	36713 36713	16908 16908	16330 16330	15378 15378
PubChem	5893 5893	15818 440143 15818 440143	439153 439153	10635 10635	1038 1038

1hdcA	Unbound	Unbound	Unbound	Analogue:CBO
1hdcB	Unbound	Unbound	Unbound	Analogue:CBO
1hdcC	Unbound	Unbound	Unbound	Analogue:CBO
1hdcD	Unbound	Unbound	Unbound	Analogue:CBO
2hsdA	Bound:NAD	Unbound	Unbound	Unbound
2hsdB	Bound:NAD	Unbound	Unbound	Unbound
2hsdC	Bound:NAD	Unbound	Unbound	Unbound
2hsdD	Bound:NAD	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
Swiss-prot;P19992 & literature [13]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1hdcA	SER 139;TYR 152;LYS 156
1hdcB	SER 139;TYR 152;LYS 156
1hdcC	SER 139;TYR 152;LYS 156
1hdcD	SER 139;TYR 152;LYS 156
2hsdA	SER 139;TYR 152;LYS 156
2hsdB	SER 139;TYR 152;LYS 156
2hsdC	SER 139;TYR 152;LYS 156
2hsdD	SER 139;TYR 152;LYS 156

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[12]
[13]	Fig.8b, p.632-637
[15]	Fig.3

References
[1]
Resource
Comments
Medline ID
PubMed ID	168869
Journal	Biochem J
Year	1975
Volume	145
Pages	483-9
Authors	Gibb W, Jeffery J
Title	The altered specificity of cortisone reductase with certain retroandrostan-3-one substrates.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	172381
Journal	Biochem Soc Trans
Year	1975
Volume	3
Pages	674-5
Authors	White IH, Jeffery J
Title	The functioning of a nicotinamide--adenine dinucleotide-dependent dehydrogenase and the structure adjacent to the reacting carbon atom of the substrate.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	902901
Journal	Biochem Soc Trans
Year	1977
Volume	5
Pages	723-4
Authors	White IH, Jeffery J
Title	Cortisone reductase and some small non-steroid analogues of its steroid substrates.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	6938245
Journal	Biochim Biophys Acta
Year	1980
Volume	616
Pages	143-52
Authors	Pasta P, Carrea G, Longhi R, Antonini E
Title	Renaturation and urea-induced denaturation of 20 beta-hydroxysteroid dehydrogenase studied in solution and in the immobilized state.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	6930328
Journal	Chem Pharm Bull (Tokyo)
Year	1980
Volume	28
Pages	730-6
Authors	Hayakawa T, Tanimoto T, Kawamura J
Title	Structural requirements in 20-oxo-steroids for interaction with the catalytic site of 20 beta-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	6929616
Journal	Steroids
Year	1980
Volume	35
Pages	111-8
Authors	Sweet F, Ahmed R, Morgan TE, Sweet BC
Title	Bifunctional enzyme activity at the same active site: competitive inhibition kinetics with 3 alpha/20 beta-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	6944159
Journal	Chem Pharm Bull (Tokyo)
Year	1981
Volume	29
Pages	476-84
Authors	Kawamura J, Tanimoto T, Fukuda H, Hayakawa T
Title	Structural requirements in 20-oxo-steroids for interaction with the binding site of 20beta-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	6587118
Journal	J Mol Biol
Year	1984
Volume	175
Pages	225-7
Authors	Fitzgerald PM, Duax WL, Punzi JS, Orr JC
Title	Crystallization and preliminary crystallographic study of 3 alpha, 20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	3455925
Journal	J Biol Chem
Year	1986
Volume	261
Pages	1306-8
Authors	Ghosh D, Punzi JS, Duax WL
Title	Crystals of active tetramers of 3 alpha, 20 beta-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	2064995
Journal	J Steroid Biochem Mol Biol
Year	1991
Volume	38
Pages	787-94
Authors	Ohno S, Nakajin S, Shinoda M
Title	20 beta-hydroxysteroid dehydrogenase of neonatal pig testis: 3 alpha/beta-hydroxysteroid dehydrogenase activities catalyzed by highly purified enzyme.
Related PDB
Related UniProtKB
[11]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)
Medline ID	92052211
PubMed ID	1946424
Journal	Proc Natl Acad Sci U S A
Year	1991
Volume	88
Pages	10064-8
Authors	Ghosh D, Weeks CM, Grochulski P, Duax WL, Erman M, Rimsay RL, Orr JC
Title	Three-dimensional structure of holo 3 alpha,20 beta-hydroxysteroid dehydrogenase: a member of a short-chain dehydrogenase family.
Related PDB
Related UniProtKB	P19992
[12]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	7866748
Journal	Structure
Year	1994
Volume	2
Pages	973-80
Authors	Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W
Title	Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor.
Related PDB	1hdc
Related UniProtKB
[13]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	7922040
Journal	Structure
Year	1994
Volume	2
Pages	629-40
Authors	Ghosh D, Wawrzak Z, Weeks CM, Duax WL, Erman M
Title	The refined three-dimensional structure of 3 alpha,20 beta-hydroxysteroid dehydrogenase and possible roles of the residues conserved in short-chain dehydrogenases.
Related PDB	2hsd
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID	7696141
Journal	J Steroid Biochem Mol Biol
Year	1995
Volume	52
Pages	209-18
Authors	Buczko E, Koh YC, Miyagawa Y, Dufau ML
Title	The rat 17 alpha-hydroxylase-17,20-desmolase (CYP17) active site: computerized homology modeling and site directed mutagenesis.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID	9029722
Journal	Steroids
Year	1997
Volume	62
Pages	95-100
Authors	Duax WL, Ghosh D
Title	Structure and function of steroid dehydrogenases involved in hypertension, fertility, and cancer.
Related PDB
Related UniProtKB

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.

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.

Created	Updated
2004-07-13	2011-06-21