DB code: S00551

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 S00552 S00553 S00602 S00604 S00605 S00608 S00610 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 RefSeq Pfam
P69167 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase
EC 1.1.1.53
NP_216518.1 (Protein)
NC_000962.3 (DNA/RNA sequence)
NP_336521.1 (Protein)
NC_002755.2 (DNA/RNA sequence)
YP_006515413.1 (Protein)
NC_018143.1 (DNA/RNA sequence)
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
P69167 HSD_MYCTU Androstan-3-alpha,17-beta-diol + NAD(+) = 17-beta-hydroxyandrostan-3-one + NADH. Homotetramer.

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

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
36713
16908
16330
15378
PubChem 5893
15818
440143
439153
10635
1038
1nffA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound
1nffB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound
1nfqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:AE2 Bound:NAI Unbound
1nfqB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:AE2 Bound:NAI Unbound
1nfqC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:AE2 Bound:NAI Unbound
1nfqD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:AE2 Bound:NAI Unbound
1nfrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound
1nfrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound
1nfrC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound
1nfrD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [16]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1nffA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nffB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfqB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfqC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfqD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfrC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157
1nfrD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;GLU 142;TYR 153;LYS 157

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[12]
[13]
Fig.8b, p.632-637
[15]
Fig.3
[16]
p.458-460

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
[16]
Resource
Comments
Medline ID
PubMed ID 12524453
Journal Proc Natl Acad Sci U S A
Year 2003
Volume 100
Pages 455-60
Authors Yang JK, Park MS, Waldo GS, Suh SW
Title Directed evolution approach to a structural genomics project: Rv2002 from Mycobacterium tuberculosis.
Related PDB 1nff 1nfq 1nfr
Related UniProtKB

Comments
This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, along with its homologous enzyme (S00326 in EzCatDB) and Drosophia alcohol dehydrogenase (S00319 in EzCatDB).
However, this enzyme has got an additional catalytic residue, Glu142, in addition to a classical catalytic triad composed of conserved residues, Ser, Tyr, and Lys. Moreover, the conformation of these residues, compared to that of the NAD molecule and substrate, seems to be slightly different from that of the homologous enzymes.
Glu142 seems to interact with the substrate oxygen atom, whereas Ser140 does not interact with the oxygen atom, unlike those catalytic Ser residues in the other homologous enzymes (see [16]). According to the literature [16], Glu142 might reverse the effect of Lys157, which is supposed to modulate the pKa of Tyr153 in the homologous enzymes.

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