DB code: S00229

CATH domain 3.20.20.100 : TIM Barrel Catalytic domain
E.C. 1.1.1.213
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.20.20.100 : TIM Barrel S00227 S00228

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P23457 3-alpha-hydroxysteroid dehydrogenase
3-alpha-HSD
EC 1.1.1.213
Hydroxyprostaglandin dehydrogenase
NP_612556.1 (Protein)
NM_138547.2 (DNA/RNA sequence)
PF00248 (Aldo_ket_red)
[Graphical View]

KEGG enzyme name
3alpha-hydroxysteroid dehydrogenase (A-specific)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P23457 DIDH_RAT Androsterone + NAD(P)(+) = 5-alpha-androstane- 3,17-dione + NAD(P)H. Monomer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00523 C00003 C00006 C00674 C00004 C00005 C00080
E.C.
Compound Androsterone NAD+ NADP+ 5alpha-Androstane-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 16032
15846
18009
15994
16908
16474
15378
PubChem 5879
5893
5886
222865
439289
439153
5884
1038
1afsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Analogue:TES Unbound Unbound
1afsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Analogue:TES Unbound Unbound
1lwiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound Unbound Unbound
1lwiB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound Unbound Unbound
1ralA 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.
Swiss-prot;P23457 & literature [16] & [19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1afsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 50;TYR 55;LYS 84;HIS 117
1afsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 50;TYR 55;LYS 84;HIS 117
1lwiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 50;TYR 55;LYS 84;HIS 117
1lwiB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 50;TYR 55;LYS 84;HIS 117
1ralA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 50;TYR 55;LYS 84;HIS 117

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
Scheme II, p.13509 1
[7]
Fig.4, p.2519 1
[9]
p.10710
[10]
Fig.6, p.S178-S181
[11]
Fig.7, Fig.8, Fig.10, p.513
[13]
Fig.3, p.477-481
[14]
Fig.2, Fig.5, Fig.6, p.104-105
[15]
p.804-806
[16]
Fig.6, p.9700-9702
[17]
Fig.4, p.11009-11011
[19]
Fig.4, p.215-218
[18]
Fig. 7, p.218
[23]
Fig. 6, p.666

References
[1]
Resource
Comments
Medline ID
PubMed ID 3006670
Journal Biochem J
Year 1986
Volume 233
Pages 493-7
Authors Kim HS, Minard P, Legoy MD, Thomas D
Title Inactivation of 3 alpha-hydroxysteroid dehydrogenase by superoxide radicals. Modification of histidine and cysteine residues causes the conformational change.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1793046
Journal Agents Actions
Year 1991
Volume 34
Pages 289-93
Authors Pawlowski J, Huizinga M, Penning TM
Title Isolation and partial characterization of a full-length cDNA clone for 3 alpha-hydroxysteroid dehydrogenase: a potential target enzyme for nonsteroidal anti-inflammatory drugs.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1747374
Journal Biochemistry
Year 1991
Volume 30
Pages 11553-60
Authors Askonas LJ, Penning TM
Title Development of affinity labeling agents based on nonsteroidal anti-inflammatory drugs: labeling of the nonsteroidal anti-inflammatory drug binding site of 3 alpha-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1788860
Journal Steroids
Year 1991
Volume 56
Pages 420-7
Authors Penning TM, Thronton R, Ricigliano JW
Title Clues to the development of mechanism-based inactivators of 3 alpha-hydroxysteroid dehydrogenase: comparison of steroidal and nonsteroidal Michael acceptors and epoxides.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7945717
Journal Farmaco
Year 1994
Volume 49
Pages 505-7
Authors Plescia S, Raffa D, Daidone G, Schillaci D, Maggio B
Title 3 alpha-hydroxysteroid dehydrogenase inhibitory activity of some N(3)-(1-R-4-carboxypyrazol-5-yl)-1,2,3-benzotriazin-4(3H)-one and quinazolin-4(3H)-one acids.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8175784
Journal J Biol Chem
Year 1994
Volume 269
Pages 13502-10
Authors Pawlowski JE, Penning TM
Title Overexpression and mutagenesis of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Role of cysteines and tyrosines in catalysis.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID 94195773
PubMed ID 8146147
Journal Proc Natl Acad Sci U S A
Year 1994
Volume 91
Pages 2517-21
Authors Hoog SS, Pawlowski JE, Alzari PM, Penning TM, Lewis M
Title Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily.
Related PDB 1ral
Related UniProtKB P23457
[8]
Resource
Comments
Medline ID
PubMed ID 7676484
Journal Steroids
Year 1995
Volume 60
Pages 491-6
Authors Hu Y, Sherwin PF, Covey DF
Title Synthesis of (17R)- and (17S)-17-hydroxy-14, 15-secoandrost-4-en-15-yn-3-one and the X-ray crystal structure of the (17S)-diastereomer.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS)
Medline ID 96346063
PubMed ID 8718859
Journal Biochemistry
Year 1996
Volume 35
Pages 10702-11
Authors Bennett MJ, Schlegel BP, Jez JM, Penning TM, Lewis M
Title Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+.
Related PDB 1lwi
Related UniProtKB P23457
[10]
Resource
Comments
Medline ID
PubMed ID 8943801
Journal J Endocrinol
Year 1996
Volume 150 Suppl
Pages S175-87
Authors Penning TM
Title 3 alpha-hydroxysteroid dehydrogenase: three dimensional structure and gene regulation.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8883217
Journal Steroids
Year 1996
Volume 61
Pages 508-23
Authors Penning TM, Pawlowski JE, Schlegel BP, Jez JM, Lin HK, Hoog SS, Bennett MJ, Lewis M
Title Mammalian 3 alpha-hydroxysteroid dehydrogenases.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9059665
Journal Adv Exp Med Biol
Year 1997
Volume 414
Pages 579-600
Authors Jez JM, Flynn TG, Penning TM
Title A nomenclature system for the aldo-keto reductase superfamily.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9059653
Journal Adv Exp Med Biol
Year 1997
Volume 414
Pages 475-90
Authors Penning TM
Title Hydroxysteroid dehydrogenases. New drug targets of the aldo-keto reductase superfamily.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9029723
Journal Steroids
Year 1997
Volume 62
Pages 101-11
Authors Penning TM, Bennett MJ, Smith-Hoog S, Schlegel BP, Jez JM, Lewis M
Title Structure and function of 3 alpha-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9261071
Journal Structure
Year 1997
Volume 5
Pages 799-812
Authors Bennett MJ, Albert RH, Jez JM, Ma H, Penning TM, Lewis M
Title Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase.
Related PDB 1afs
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9657682
Journal Biochemistry
Year 1998
Volume 37
Pages 9695-703
Authors Jez JM, Penning TM
Title Engineering steroid 5 beta-reductase activity into rat liver 3 alpha-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9692994
Journal Biochemistry
Year 1998
Volume 37
Pages 11003-11
Authors Schlegel BP, Ratnam K, Penning TM
Title Retention of NADPH-linked quinone reductase activity in an aldo-keto reductase following mutation of the catalytic tyrosine.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10549852
Journal Biol Pharm Bull
Year 1999
Volume 22
Pages 1038-46
Authors Yamano S, Ichinose F, Todaka T, Toki S
Title Purification and characterization of two major forms of naloxone reductase from rabbit liver cytosol, new members of aldo-keto reductase superfamily.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10418995
Journal J Steroid Biochem Mol Biol
Year 1999
Volume 69
Pages 211-25
Authors Penning TM
Title Molecular determinants of steroid recognition and catalysis in aldo-keto reductases. Lessons from 3alpha-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10500147
Journal Proc Natl Acad Sci U S A
Year 1999
Volume 96
Pages 11161-6
Authors Ma H, Penning TM
Title Conversion of mammalian 3alpha-hydroxysteroid dehydrogenase to 20alpha-hydroxysteroid dehydrogenase using loop chimeras: changing specificity from androgens to progestins.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10998348
Journal Biochem J
Year 2000
Volume 351
Pages 67-77
Authors Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K
Title Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10876166
Journal J Biochem (Tokyo)
Year 2000
Volume 128
Pages 121-8
Authors Yamamoto T, Nozaki A, Shintani S, Ishikura S, Katagiri Y, Hara A
Title Structure-specific effects of thyroxine analogs on human liver 3 alpha-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11306084
Journal Chem Biol Interact
Year 2001
Volume 130-132
Pages 659-71
Authors Penning TM, Ma H, Jez JM
Title Engineering steroid hormone specificity into aldo-keto reductases.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11165022
Journal Mol Cell Endocrinol
Year 2001
Volume 171
Pages 137-49
Authors Penning TM, Burczynski ME, Jez JM, Lin HK, Ma H, Moore M, Ratnam K, Palackal N
Title Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3).
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12943710
Journal J Steroid Biochem Mol Biol
Year 2003
Volume 85
Pages 247-55
Authors Penning TM, Jin Y, Heredia VV, Lewis M
Title Structure-function relationships in 3alpha-hydroxysteroid dehydrogenases: a comparison of the rat and human isoforms.
Related PDB
Related UniProtKB

Comments
This enzyme has been transferred from E.C.1.1.1.50 (B-specific) to E.C.1.1.1.213 (A-specific) (see [9]).

Created Updated
2004-02-02 2009-02-26