EzCatDB: S00327
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DB codeS00327
RLCP classification9.1050.440000.8010 : Hydride transfer
9.5010.536200.8010 : Hydride transfer
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
E.C.1.1.1.62

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,S00326,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

P14061Q8NBQ5
Protein nameEstradiol 17-beta-dehydrogenase 1Estradiol 17-beta-dehydrogenase 11estradiol 17beta-dehydrogenase
20alpha-hydroxysteroid dehydrogenase
17beta,20alpha-hydroxysteroid dehydrogenase
17beta-estradiol dehydrogenase
estradiol dehydrogenase
estrogen 17-oxidoreductase
17beta-HSD
SynonymsEC 1.1.1.62
17-beta-hydroxysteroid dehydrogenase type 1
17-beta-HSD 1
Placental 17-beta-hydroxysteroid dehydrogenase
20 alpha-hydroxysteroid dehydrogenase
20-alpha-HSD
E2DH
EC 1.1.1.62
17-beta-hydroxysteroid dehydrogenase 11
17-beta-HSD 11
17betaHSD11
17bHSD11
17-beta-HSD XI
17betaHSDXI
Dehydrogenase/reductase SDR family member 8
Retinal short-chain dehydrogenase/reductase 2
retSDR2
Cutaneous T-cell lymphoma-associated antigen HD-CL-03
CTCL tumor antigen HD-CL-03
RefSeqNP_000404.2 (Protein)
NM_000413.2 (DNA/RNA sequence)
NP_057329.2 (Protein)
NM_016245.3 (DNA/RNA sequence)
PfamPF00106 (adh_short)
[Graphical view]
PF00106 (adh_short)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00150Androgen and estrogen metabolism

UniProtKB:Accession NumberP14061Q8NBQ5
Entry nameDHB1_HUMANDHB11_HUMAN
ActivityEstradiol-17-beta + NAD(P)(+) = estrone + NAD(P)H.Estradiol-17-beta + NAD(P)(+) = estrone + NAD(P)H.
SubunitHomodimer.
Subcellular locationCytoplasm.Secreted (Potential).
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00003C00006C00951C00004C00005C00468C00080
CompoundNAD+NADP+Estradiol-17betaNADHNADPHEstroneH+
Typeamide group,amine group,nucleotideamide group,amine group,nucleotidearomatic ring (only carbon atom),carbohydrate,steroidamide group,amine group,nucleotideamide group,amine group,nucleotidearomatic ring (only carbon atom),carbohydrate,steroidothers
ChEBI15846
18009
16469
16908
16474
17263
15378
PubChem5893
5886
5757
439153
5884
5870
1038
               
1a27AUnboundBound:NAPBound:ESTUnboundUnboundUnbound 
1bhsAUnboundUnboundUnboundUnboundUnboundUnbound 
1dhtAUnboundUnboundAnalogue:DHTUnboundUnboundUnbound 
1equAUnboundBound:NAPUnboundUnboundUnboundAnalogue:EQI 
1equBUnboundBound:NAPUnboundUnboundUnboundUnbound 
1fdsAUnboundUnboundBound:ESTUnboundUnboundUnbound 
1fdtAUnboundBound:NAPBound:ESTUnboundUnboundUnbound 
1fduAUnboundBound:NAPBound:ESTUnboundUnboundUnbound 
1fduBUnboundBound:NAPBound:ESTUnboundUnboundUnbound 
1fduCUnboundBound:NAPBound:ESTUnboundUnboundUnbound 
1fduDUnboundBound:NAPBound:ESTUnboundUnboundUnbound 
1fdvABound:NADUnboundUnboundUnboundUnboundUnbound 
1fdvBBound:NADUnboundUnboundUnboundUnboundUnbound 
1fdvCBound:NADUnboundUnboundUnboundUnboundUnbound 
1fdvDBound:NADUnboundUnboundUnboundUnboundUnbound 
1fdwAUnboundUnboundBound:ESTUnboundUnboundUnbound 
1i5rAAnalogue:HYC(Adenosine of NAD)UnboundAnalogue:HYC(Estradiol)UnboundUnboundUnbound 
1iolAUnboundUnboundBound:ESTUnboundUnboundUnbound 
1jtvAUnboundUnboundAnalogue:TES(disoriented)UnboundUnboundUnbound 
1qyvAUnboundBound:NAPUnboundUnboundUnboundUnbound 
1qywAUnboundAnalogue:NAPUnboundUnboundUnboundAnalogue:5SD(disoriented) 
1qyxAUnboundAnalogue:NAPUnboundUnboundUnboundAnalogue:ASD(disoriented) 
3deyXUnboundUnboundAnalogue:DHT(disoriented)UnboundUnboundUnbound 
3dheAUnboundUnboundUnboundUnboundUnboundAnalogue:AND 
3hb4XUnboundUnboundAnalogue:E2BUnboundUnboundUnbound 
3hb5XUnboundBound:NAPAnalogue:E2BUnboundUnboundUnbound 
3klmXUnboundUnboundAnalogue:DHT(disoriented)UnboundUnboundUnbound 
3klpXUnboundUnboundAnalogue:B81(disoriented)UnboundUnboundUnbound 
3km0AUnboundBound:NAPAnalogue:AOMUnboundUnboundUnbound 
3km0BUnboundBound:NAPAnalogue:AOMUnboundUnboundUnbound 
1yb1AUnboundUnboundUnboundUnboundUnboundAnalogue:AE2(disoriented) 
1yb1BUnboundUnboundUnboundUnboundUnboundAnalogue:AE2(disoriented) 

Active-site residues
resource
Swiss-prot;P14061 & literature [16], [19] & [20]
pdbCatalytic residuescomment
          
1a27ASER 142;TYR 155;LYS 159
 
1bhsASER 142;TYR 155;LYS 159
 
1dhtASER 142;TYR 155;LYS 159
 
1equASER 142;TYR 155;LYS 159
 
1equBSER 142;TYR 155;LYS 159
 
1fdsASER 142;TYR 155;LYS 159
 
1fdtASER 142;TYR 155;LYS 159
 
1fduASER 142;TYR 155;LYS 159
mutant H221L
1fduBSER 142;TYR 155;LYS 159
mutant H221L
1fduCSER 142;TYR 155;LYS 159
mutant H221L
1fduDSER 142;TYR 155;LYS 159
mutant H221L
1fdvASER 142;TYR 155;LYS 159
mutant H221L
1fdvBSER 142;TYR 155;LYS 159
mutant H221L
1fdvCSER 142;TYR 155;LYS 159
mutant H221L
1fdvDSER 142;TYR 155;LYS 159
mutant H221L
1fdwASER 142;TYR 155;LYS 159
mutant H221Q
1i5rASER 142;TYR 155;LYS 159
 
1iolASER 142;TYR 155;LYS 159
 
1jtvASER 142;TYR 155;LYS 159
 
1qyvASER 142;TYR 155;LYS 159
 
1qywASER 142;TYR 155;LYS 159
 
1qyxASER 142;TYR 155;LYS 159
 
3deyXSER 142;TYR 155;LYS 159
 
3dheASER 142;TYR 155;LYS 159
 
3hb4XSER 142;TYR 155;LYS 159
 
3hb5XSER 142;TYR 155;LYS 159
 
3klmXSER 142;TYR 155;LYS 159
 
3klpXSER 142;TYR 155;LYS 159
 
3km0ASER 142;TYR 155;LYS 159
 
3km0BSER 142;TYR 155;LYS 159
 
1yb1ASER 167;TYR 180;LYS 184
 
1yb1BSER 167;TYR 180;LYS 184
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[13]Fig.1, p.1061-1062
[14]Fig.1, p.200-201
[16]Fig.7, p.505-508
[18]Fig.5, p.S19
[19]p.667-668
[20]Fig.7, p.910-913
[26]Fig.2, p.841-842
[28]p.1109

references
[1]
PubMed ID240714
JournalEur J Biochem
Year1975
Volume56
Pages557-61
AuthorsBiellmann JF, Hirth CG
TitleNAD(P)+ analogues: tools for the investigation of the active site of oestradiol 17beta-dehydrogenase from human placenta.
[2]
PubMed ID976263
JournalEur J Biochem
Year1976
Volume68
Pages385-94
AuthorsPons M, Nicolas JC, Boussioux AM, Descomps B, Crastes de Paulet A
TitleAffinity labelling of the estradiol-17 beta dehydrogenase from human placenta with substrate analogs.
[3]
PubMed ID570483
JournalEndocrinology
Year1978
Volume102
Pages1398-1403
AuthorsTseng L
TitleSteroid specificity in the stimulation of human endometrial estradiol dehydrogenase.
[4]
PubMed ID6949898
JournalJ Biol Chem
Year1982
Volume257
Pages2225-9
AuthorsChin CC, Pineda J, Warren JC
TitleSpatial relationship of steroid and cofactor at the active site of human placental estradiol 17 beta-dehydrogenase.
[5]
PubMed ID6949900
JournalJ Biol Chem
Year1982
Volume257
Pages2783-6
AuthorsTobias B, Covey DF, Strickler RC
TitleInactivation of human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase with active site-directed 17 beta-propynyl-substituted progestin analogs.
[6]
PubMed ID6572146
JournalEur J Biochem
Year1983
Volume129
Pages691-5
AuthorsInano H, Tamaoki B
TitleAffinity labeling of arginyl residues at the catalytic region of estradiol 17 beta-dehydrogenase from human placenta by 16-oxoestrone.
[7]
PubMed ID6580513
JournalJ Steroid Biochem
Year1983
Volume19
Pages1617-22
AuthorsInano H, Ohba H, Tamaoki B
TitlePhotochemical inactivation of human placental estradiol 17 beta-dehydrogenase in the presence of 2,3-butanedione.
[8]
PubMed ID3456799
JournalBiochemistry
Year1986
Volume25
Pages641-6
AuthorsMurdock GL, Chin CC, Warren JC
TitleHuman placental estradiol 17 beta-dehydrogenase: sequence of a histidine-bearing peptide in the catalytic region.
[9]
PubMed ID3130054
JournalBiochem Biophys Res Commun
Year1988
Volume152
Pages789-93
AuthorsInano H
TitleChemical modification of lysine residues at active-site of human placental estradiol 17 beta-dehydrogenase.
[10]
PubMed ID2846351
JournalFEBS Lett
Year1988
Volume239
Pages73-7
AuthorsPeltoketo H, Isomaa V, Maentausta O, Vihko R
TitleComplete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA.
[11]
PubMed ID2772972
JournalSteroids
Year1989
Volume53
Pages77-96
AuthorsAuchus RJ, Palmer JO, Carrell HL, Covey DF
TitlePreparation of 14,15-secoestra-1,3,5(10)-trien-15-ynes, inhibitors of estradiol dehydrogenase.
[12]
PubMed ID2146972
JournalJ Steroid Biochem Mol Biol
Year1990
Volume37
Pages65-70
AuthorsPineda JA, Murdock GL, Watson RJ, Warren JC
TitleStereospecificity of hydrogen transfer between progesterone and cofactor by human placental estradiol-17 beta dehydrogenase.
[13]
PubMed ID1953709
JournalBiochem Biophys Res Commun
Year1991
Volume180
Pages1057-63
AuthorsSweet F, Boyd J, Medina O, Konderski L, Murdock GL
TitleHydrogen bonding in steroidogenesis: studies on new heterocyclic analogs of estrone that inhibit human estradiol 17 beta-dehydrogenase.
[14]
PubMed ID1998720
JournalBiochim Biophys Acta
Year1991
Volume1076
Pages197-202
AuthorsMurdock GL, Pineda J, Nagorsky N, Lawrence SS, Heritage R, Warren JC
TitleEstradiol 17 beta-dehydrogenase: full enzymatic activity in the absence of zinc.
[15]
PubMed ID8200347
JournalEur J Biochem
Year1994
Volume222
Pages221-7
AuthorsLeenders F, Adamski J, Husen B, Thole HH, Jungblut PW
TitleMolecular cloning and amino acid sequence of the porcine 17 beta-estradiol dehydrogenase.
[16]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 AND 1.7 ANGSTROMS).
Medline ID95393021
PubMed ID7663947
JournalStructure
Year1995
Volume3
Pages503-13
AuthorsGhosh D, Pletnev VZ, Zhu DW, Wawrzak Z, Duax WL, Pangborn W, Labrie F, Lin SX
TitleStructure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 A resolution.
Related PDB1bhs
Related UniProtKBP14061
[17]
PubMed ID8917625
JournalBiochim Biophys Acta
Year1996
Volume1297
Pages219-27
AuthorsMendoza-Hernandez G, Rendon JL
TitleHuman placental estradiol 17 beta-dehydrogenase: structural and catalytic changes during urea denaturation.
[18]
PubMed ID8943782
JournalJ Endocrinol
Year1996
Volume150 Suppl
PagesS13-20
AuthorsLin SX, Zhu DW, Azzi A, Campbell RL, Breton R, Labrie F, Ghosh D, Pletnev V, Duax WL, Pangborn W
TitleStudies on the three-dimensional structure of estrogenic 17 beta-hydroxysteroid dehydrogenase.
[19]
CommentsX-ray crystallography
PubMed ID8756321
JournalNat Struct Biol
Year1996
Volume3
Pages665-8
AuthorsAzzi A, Rehse PH, Zhu DW, Campbell RL, Labrie F, Lin SX
TitleCrystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase complexed with 17 beta-estradiol.
Related PDB1iol
[20]
CommentsX-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
Medline ID96398680
PubMed ID8805577
JournalStructure
Year1996
Volume4
Pages905-15
AuthorsBreton R, Housset D, Mazza C, Fontecilla-Camps JC
TitleThe structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors.
Related PDB1fds,1fdt
Related UniProtKBP14061
[21]
CommentsX-ray crystallography
JournalGrenoble : Universite Joseph Fourier (Thesis)
Year1997
Volume
Pages
AuthorsMazza, C
TitleHuman Type I 17Beta-Hydroxysteroid Dehydrogenase: Site Directed Mutagenesis and X-Ray Crystallography Structure-Function Analysis.
Related PDB1a27
[22]
PubMed ID8994190
JournalMol Endocrinol
Year1997
Volume11
Pages77-86
AuthorsPuranen T, Poutanen M, Ghosh D, Vihko P, Vihko R
TitleCharacterization of structural and functional properties of human 17 beta-hydroxysteroid dehydrogenase type 1 using recombinant enzymes and site-directed mutagenesis.
[23]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID98192605
PubMed ID9525918
JournalJ Biol Chem
Year1998
Volume273
Pages8145-52
AuthorsMazza C, Breton R, Housset D, Fontecilla-Camps JC
TitleUnusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase.
Related PDB1fdu,1fdv,1fdw
Related UniProtKBP14061
[24]
PubMed ID10419021
JournalJ Steroid Biochem Mol Biol
Year1999
Volume69
Pages425-9
AuthorsLin SX, Han Q, Azzi A, Zhu DW, Gangloff A, Campbell RL, Gongloff A
Title3D-structure of human estrogenic 17beta-HSD1: binding with various steroids.
[25]
PubMed ID10622412
JournalJ Steroid Biochem Mol Biol
Year1999
Volume70
Pages229-35
AuthorsZhu DW, Campbell R, Labrie F, Lin SX
TitleCrystallization and preliminary crystal structure of the complex of 17beta-hydroxysteroid dehydrogenase with a dual-site inhibitor.
[26]
CommentsX-ray crystallography
PubMed ID9927655
JournalProc Natl Acad Sci U S A
Year1999
Volume96
Pages840-5
AuthorsSawicki MW, Erman M, Puranen T, Vihko P, Ghosh D
TitleStructure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+.
Related PDB1equ
[27]
PubMed ID11368312
JournalArch Biochem Biophys
Year2000
Volume384
Pages255-62
AuthorsRizner TL, Adamski J, Stojan J
Title17Beta-hydroxysteroid dehydrogenase from Cochliobolus lunatus: model structure and substrate specificity.
[28]
CommentsX-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 38-327, AND MUTAGENESIS OF LEU-149.
PubMed ID10625652
JournalJ Biol Chem
Year2000
Volume275
Pages1105-11
AuthorsHan Q, Campbell RL, Gangloff A, Huang YW, Lin SX
TitleDehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid discrimination and enzyme-induced strain.
Related PDB1dht,3dhe
[29]
PubMed ID11719564
JournalMol Biol Evol
Year2001
Volume18
Pages2154-61
AuthorsBreitling R, Laubner D, Adamski J
TitleStructure-based phylogenetic analysis of short-chain alcohol dehydrogenases and reclassification of the 17beta-hydroxysteroid dehydrogenase family.
[30]
PubMed ID11682630
JournalMol Endocrinol
Year2001
Volume15
Pages2010-20
AuthorsHuang YW, Pineau I, Chang HJ, Azzi A, Bellemare V, Laberge S, Lin SX
TitleCritical residues for the specificity of cofactors and substrates in human estrogenic 17beta-hydroxysteroid dehydrogenase 1: variants designed from the three-dimensional structure of the enzyme.
[31]
PubMed ID12475215
JournalBiochemistry
Year2002
Volume41
Pages14659-68
AuthorsBenach J, Filling C, Oppermann UC, Roversi P, Bricogne G, Berndt KD, Jornvall H, Ladenstein R
TitleStructure of bacterial 3beta/17beta-hydroxysteroid dehydrogenase at 1.2 A resolution: a model for multiple steroid recognition.
[32]
CommentsX-ray crystallography
PubMed ID12223444
JournalFASEB J
Year2002
Volume16
Pages1829-31
AuthorsQiu W, Campbell RL, Gangloff A, Dupuis P, Boivin RP, Tremblay MR, Poirier D, Lin SX
TitleA concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity.
Related PDB1i5r
[33]
PubMed ID12604234
JournalChem Biol Interact
Year2003
Volume143-144
Pages481-91
AuthorsBrown WM, Metzger LE, Barlow JP, Hunsaker LA, Deck LM, Royer RE, Vander Jagt DL
Title17-beta-Hydroxysteroid dehydrogenase type 1: computational design of active site inhibitors targeted to the Rossmann fold.
[34]
CommentsX-ray crystallography
PubMed ID12490543
JournalFASEB J
Year2003
Volume17
Pages274-6
AuthorsGangloff A, Shi R, Nahoum V, Lin SX
TitlePseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase.
Related PDB1jtv
[35]
PubMed ID15110763
JournalBiochem Biophys Res Commun
Year2004
Volume318
Pages131-4
AuthorsOwen CP, Ahmed S
TitleThe derivation of a potential transition state for the reduction reaction catalysed by 17beta-hydroxysteroid dehydrogenase--an approximate representation of its active site for use in drug design and discovery.
[36]
PubMed ID14966133
JournalJ Biol Chem
Year2004
Volume279
Pages16778-85
AuthorsShi R, Lin SX
TitleCofactor hydrogen bonding onto the protein main chain is conserved in the short chain dehydrogenase/reductase family and contributes to nicotinamide orientation.
Related PDB1qyv,1qyw,1qyx
[37]
PubMed ID16414178
JournalMol Cell Endocrinol
Year2006
Volume248
Pages61-71
AuthorsLukacik P, Kavanagh KL, Oppermann U
TitleStructure and function of human 17beta-hydroxysteroid dehydrogenases.
Related PDB1yb1
[38]
PubMed ID19929851
JournalBiochem J
Year2009
Volume424
Pages357-66
AuthorsMazumdar M, Fournier D, Zhu DW, Cadot C, Poirier D, Lin SX
TitleBinary and ternary crystal structure analyses of a novel inhibitor with 17beta-HSD type 1: a lead compound for breast cancer therapy.
Related PDB3hb4,3hb5
[39]
PubMed ID20172961
JournalMol Endocrinol
Year2010
Volume24
Pages832-45
AuthorsAka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX
Title17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production.
Related PDB3dey,3klm

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, its catalytic mechanism must be similar to those of the homologous enzymes.
According to the literature [37], type 1 of this enzyme (17-beta-hydroxysteroid dehydrogenase) (Swiss-prot;P14061) catalyzes the reduction of estrone to estradiol-17-beta, whereas type 11 (Swiss-prot;Q8NBQ5) catalyzes the oxidation/dehydrogenation of 5-alpha-androstanediol to androstrone.

createdupdated
2004-07-132011-06-24
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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