EzCatDB: S00229
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DB codeS00229
CATH domainDomain 13.20.20.100 : TIM BarrelCatalytic domain
E.C.1.1.1.213

CATH domainRelated DB codes (homologues)
3.20.20.100 : TIM BarrelS00227,S00228

Enzyme Name
UniProtKBKEGG

P23457
Protein name3-alpha-hydroxysteroid dehydrogenase3alpha-hydroxysteroid dehydrogenase (A-specific)
Synonyms3-alpha-HSD
EC 1.1.1.213
Hydroxyprostaglandin dehydrogenase
RefSeqNP_612556.1 (Protein)
NM_138547.2 (DNA/RNA sequence)
PfamPF00248 (Aldo_ket_red)
[Graphical view]


UniProtKB:Accession NumberP23457
Entry nameDIDH_RAT
ActivityAndrosterone + NAD(P)(+) = 5-alpha-androstane- 3,17-dione + NAD(P)H.
SubunitMonomer.
Subcellular locationCytoplasm.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00523C00003C00006C00674C00004C00005C00080
CompoundAndrosteroneNAD+NADP+5alpha-Androstane-3,17-dioneNADHNADPHH+
Typecarbohydrate,steroidamide group,amine group,nucleotideamide group,amine group,nucleotidecarbohydrate,steroidamide group,amine group,nucleotideamide group,amine group,nucleotideothers
ChEBI16032
15846
18009
15994
16908
16474
15378
PubChem5879
5893
5886
439289
222865
439153
5884
1038
               
1afsAUnboundUnboundBound:NAPAnalogue:TESUnboundUnbound 
1afsBUnboundUnboundBound:NAPAnalogue:TESUnboundUnbound 
1lwiAUnboundUnboundBound:NAPUnboundUnboundUnbound 
1lwiBUnboundUnboundBound:NAPUnboundUnboundUnbound 
1ralAUnboundUnboundUnboundUnboundUnboundUnbound 

Active-site residues
resource
Swiss-prot;P23457 & literature [16] & [19]
pdbCatalytic residues
         
1afsAASP 50;TYR 55;LYS 84;HIS 117
1afsBASP 50;TYR 55;LYS 84;HIS 117
1lwiAASP 50;TYR 55;LYS 84;HIS 117
1lwiBASP 50;TYR 55;LYS 84;HIS 117
1ralAASP 50;TYR 55;LYS 84;HIS 117

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]Scheme II, p.135091
[7]Fig.4, p.25191
[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]
PubMed ID3006670
JournalBiochem J
Year1986
Volume233
Pages493-7
AuthorsKim HS, Minard P, Legoy MD, Thomas D
TitleInactivation of 3 alpha-hydroxysteroid dehydrogenase by superoxide radicals. Modification of histidine and cysteine residues causes the conformational change.
[2]
PubMed ID1793046
JournalAgents Actions
Year1991
Volume34
Pages289-93
AuthorsPawlowski J, Huizinga M, Penning TM
TitleIsolation and partial characterization of a full-length cDNA clone for 3 alpha-hydroxysteroid dehydrogenase: a potential target enzyme for nonsteroidal anti-inflammatory drugs.
[3]
PubMed ID1747374
JournalBiochemistry
Year1991
Volume30
Pages11553-60
AuthorsAskonas LJ, Penning TM
TitleDevelopment of affinity labeling agents based on nonsteroidal anti-inflammatory drugs: labeling of the nonsteroidal anti-inflammatory drug binding site of 3 alpha-hydroxysteroid dehydrogenase.
[4]
PubMed ID1788860
JournalSteroids
Year1991
Volume56
Pages420-7
AuthorsPenning TM, Thronton R, Ricigliano JW
TitleClues to the development of mechanism-based inactivators of 3 alpha-hydroxysteroid dehydrogenase: comparison of steroidal and nonsteroidal Michael acceptors and epoxides.
[5]
PubMed ID7945717
JournalFarmaco
Year1994
Volume49
Pages505-7
AuthorsPlescia S, Raffa D, Daidone G, Schillaci D, Maggio B
Title3 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.
[6]
PubMed ID8175784
JournalJ Biol Chem
Year1994
Volume269
Pages13502-10
AuthorsPawlowski JE, Penning TM
TitleOverexpression and mutagenesis of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Role of cysteines and tyrosines in catalysis.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID94195773
PubMed ID8146147
JournalProc Natl Acad Sci U S A
Year1994
Volume91
Pages2517-21
AuthorsHoog SS, Pawlowski JE, Alzari PM, Penning TM, Lewis M
TitleThree-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily.
Related PDB1ral
Related UniProtKBP23457
[8]
PubMed ID7676484
JournalSteroids
Year1995
Volume60
Pages491-6
AuthorsHu Y, Sherwin PF, Covey DF
TitleSynthesis 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.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS)
Medline ID96346063
PubMed ID8718859
JournalBiochemistry
Year1996
Volume35
Pages10702-11
AuthorsBennett MJ, Schlegel BP, Jez JM, Penning TM, Lewis M
TitleStructure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+.
Related PDB1lwi
Related UniProtKBP23457
[10]
PubMed ID8943801
JournalJ Endocrinol
Year1996
Volume150 Suppl
PagesS175-87
AuthorsPenning TM
Title3 alpha-hydroxysteroid dehydrogenase: three dimensional structure and gene regulation.
[11]
PubMed ID8883217
JournalSteroids
Year1996
Volume61
Pages508-23
AuthorsPenning TM, Pawlowski JE, Schlegel BP, Jez JM, Lin HK, Hoog SS, Bennett MJ, Lewis M
TitleMammalian 3 alpha-hydroxysteroid dehydrogenases.
[12]
PubMed ID9059665
JournalAdv Exp Med Biol
Year1997
Volume414
Pages579-600
AuthorsJez JM, Flynn TG, Penning TM
TitleA nomenclature system for the aldo-keto reductase superfamily.
[13]
PubMed ID9059653
JournalAdv Exp Med Biol
Year1997
Volume414
Pages475-90
AuthorsPenning TM
TitleHydroxysteroid dehydrogenases. New drug targets of the aldo-keto reductase superfamily.
[14]
PubMed ID9029723
JournalSteroids
Year1997
Volume62
Pages101-11
AuthorsPenning TM, Bennett MJ, Smith-Hoog S, Schlegel BP, Jez JM, Lewis M
TitleStructure and function of 3 alpha-hydroxysteroid dehydrogenase.
[15]
CommentsX-ray crystallography
PubMed ID9261071
JournalStructure
Year1997
Volume5
Pages799-812
AuthorsBennett MJ, Albert RH, Jez JM, Ma H, Penning TM, Lewis M
TitleSteroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase.
Related PDB1afs
[16]
PubMed ID9657682
JournalBiochemistry
Year1998
Volume37
Pages9695-703
AuthorsJez JM, Penning TM
TitleEngineering steroid 5 beta-reductase activity into rat liver 3 alpha-hydroxysteroid dehydrogenase.
[17]
PubMed ID9692994
JournalBiochemistry
Year1998
Volume37
Pages11003-11
AuthorsSchlegel BP, Ratnam K, Penning TM
TitleRetention of NADPH-linked quinone reductase activity in an aldo-keto reductase following mutation of the catalytic tyrosine.
[18]
PubMed ID10549852
JournalBiol Pharm Bull
Year1999
Volume22
Pages1038-46
AuthorsYamano S, Ichinose F, Todaka T, Toki S
TitlePurification and characterization of two major forms of naloxone reductase from rabbit liver cytosol, new members of aldo-keto reductase superfamily.
[19]
PubMed ID10418995
JournalJ Steroid Biochem Mol Biol
Year1999
Volume69
Pages211-25
AuthorsPenning TM
TitleMolecular determinants of steroid recognition and catalysis in aldo-keto reductases. Lessons from 3alpha-hydroxysteroid dehydrogenase.
[20]
PubMed ID10500147
JournalProc Natl Acad Sci U S A
Year1999
Volume96
Pages11161-6
AuthorsMa H, Penning TM
TitleConversion of mammalian 3alpha-hydroxysteroid dehydrogenase to 20alpha-hydroxysteroid dehydrogenase using loop chimeras: changing specificity from androgens to progestins.
[21]
PubMed ID10998348
JournalBiochem J
Year2000
Volume351
Pages67-77
AuthorsPenning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K
TitleHuman 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.
[22]
PubMed ID10876166
JournalJ Biochem (Tokyo)
Year2000
Volume128
Pages121-8
AuthorsYamamoto T, Nozaki A, Shintani S, Ishikura S, Katagiri Y, Hara A
TitleStructure-specific effects of thyroxine analogs on human liver 3 alpha-hydroxysteroid dehydrogenase.
[23]
PubMed ID11306084
JournalChem Biol Interact
Year2001
Volume130-132
Pages659-71
AuthorsPenning TM, Ma H, Jez JM
TitleEngineering steroid hormone specificity into aldo-keto reductases.
[24]
PubMed ID11165022
JournalMol Cell Endocrinol
Year2001
Volume171
Pages137-49
AuthorsPenning TM, Burczynski ME, Jez JM, Lin HK, Ma H, Moore M, Ratnam K, Palackal N
TitleStructure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3).
[25]
PubMed ID12943710
JournalJ Steroid Biochem Mol Biol
Year2003
Volume85
Pages247-55
AuthorsPenning TM, Jin Y, Heredia VV, Lewis M
TitleStructure-function relationships in 3alpha-hydroxysteroid dehydrogenases: a comparison of the rat and human isoforms.

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]).

createdupdated
2004-02-022009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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