EzCatDB: S00543
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DB codeS00543
RLCP classification9.5010.536200.8010 : Hydride transfer
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
E.C.1.1.1.184,1.1.1.189,1.1.1.197

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00551,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

Enzyme Name
UniProtKBKEGG

Q28960P16152
Protein nameCarbonyl reductase [NADPH] 1Carbonyl reductase [NADPH] 1carbonyl reductase (NADPH)
   (EC 1.1.1.184)

aldehyde reductase 1
   (EC 1.1.1.184)

prostaglandin 9-ketoreductase
   (EC 1.1.1.184)

xenobiotic ketone reductase
   (EC 1.1.1.184)

NADPH-dependent carbonyl reductase
   (EC 1.1.1.184)

ALR3
   (EC 1.1.1.184)

carbonyl reductase
   (EC 1.1.1.184)

nonspecific NADPH-dependent carbonyl reductase
   (EC 1.1.1.184)

aldehyde reductase 1
   (EC 1.1.1.184)

carbonyl reductase (NADPH)
   (EC 1.1.1.184)

prostaglandin-E2 9-reductase
   (EC 1.1.1.189)

PGE2-9-OR
   (EC 1.1.1.189)

reductase, 15-hydroxy-9-oxoprostaglandin
   (EC 1.1.1.189)

9-keto-prostaglandin E2 reductase
   (EC 1.1.1.189)

9-ketoprostaglandin reductase
   (EC 1.1.1.189)

PGE-9-ketoreductase
   (EC 1.1.1.189)

PGE2 9-oxoreductase
   (EC 1.1.1.189)

PGE2-9-ketoreductase
   (EC 1.1.1.189)

prostaglandin 9-ketoreductase
   (EC 1.1.1.189)

prostaglandin E 9-ketoreductase
   (EC 1.1.1.189)

prostaglandin E2-9-oxoreductase
   (EC 1.1.1.189)

15-hydroxyprostaglandin dehydrogenase (NADP+)
   (EC 1.1.1.197)

NADP+-dependent 15-hydroxyprostaglandin dehydrogenase
   (EC 1.1.1.197)

NADP+-linked 15-hydroxyprostaglandin dehydrogenase
   (EC 1.1.1.197)

NADP+-specific 15-hydroxyprostaglandin dehydrogenase
   (EC 1.1.1.197)

type II 15-hydroxyprostaglandin dehydrogenase
   (EC 1.1.1.197)

15-hydroxyprostaglandin dehydrogenase (NADP+)
   (EC 1.1.1.197)

SynonymsEC 1.1.1.184
NADPH-dependent carbonyl reductase 1
20-beta-hydroxysteroid dehydrogenase
Prostaglandin-E(2) 9-reductase
EC 1.1.1.189
Prostaglandin 9-ketoreductase
15-hydroxyprostaglandin dehydrogenase [NADP+]
EC 1.1.1.197
EC 1.1.1.184
NADPH-dependent carbonyl reductase 1
Prostaglandin-E(2) 9-reductase
EC 1.1.1.189
Prostaglandin 9-ketoreductase
15-hydroxyprostaglandin dehydrogenase [NADP+]
EC 1.1.1.197
RefSeqNP_999238.1 (Protein)
NM_214073.1 (DNA/RNA sequence)
NP_001748.1 (Protein)
NM_001757.2 (DNA/RNA sequence)
PfamPF00106 (adh_short)
[Graphical view]
PF00106 (adh_short)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00590Arachidonic acid metabolism1.1.1.184,1.1.1.189

UniProtKB:Accession NumberQ28960P16152
Entry nameCBR1_PIGCBR1_HUMAN
ActivityR-CHOH-R'' + NADP(+) = R-CO-R'' + NADPH.,(13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-13-enoate + NADP(+) = (13E)-11-alpha-hydroxy-9,15-dioxoprost-13-enoate + NADPH.,(5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate + NADPH.R-CHOH-R' + NADP(+) = R-CO-R' + NADPH.,(5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate + NADPH.,(13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-13-enoate + NADP(+) = (13E)-11-alpha-hydroxy-9,15-dioxoprost-13-enoate + NADPH.
SubunitMonomer.Monomer.
Subcellular locationCytoplasm (By similarity).Cytoplasm.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00005C00080C01450C00584C04654C00006C01612C00639C04741
E.C.1.1.1.184,1.1.1.189,1.1.1.1971.1.1.184,1.1.1.189,1.1.1.1971.1.1.1841.1.1.1891.1.1.1971.1.1.184,1.1.1.189,1.1.1.1971.1.1.1841.1.1.1891.1.1.197
CompoundNADPHH+R-CO-R'(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate(13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoateNADP+R-CHOH-R'(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate(13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate
Typeamide group,amine group,nucleotideotherscarbohydratecarbohydrate,fatty acid,lipidcarbohydrate,fatty acid,lipidamide group,amine group,nucleotidecarbohydratecarbohydrate,fatty acid,lipidcarbohydrate,fatty acid,lipid
ChEBI16474
15378

15551
15548
18009

15553
15544
PubChem5884
1038

5280360
5280710
5886

5280363
5280723
                 
1hu4ABound:NDP UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1n5dABound:NDP UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1wmaABound:NDP Analogue:AB3 307UnboundUnboundUnboundUnboundUnboundUnbound
2pfgAUnbound Analogue:DDDUnboundUnboundBound:NAPUnboundUnboundUnbound
3bhiAUnbound UnboundUnboundUnboundBound:NAPUnboundUnboundUnbound
3bhjAUnbound Analogue:AB3 307UnboundUnboundBound:NAPUnboundUnboundUnbound
3bhmAUnbound Analogue:AB3 307UnboundUnboundBound:NAPUnboundUnboundUnbound

Active-site residues
resource
literature [16], [19]
pdbCatalytic residues
         
1hu4ASER 139;TYR 193;LYS 197
1n5dASER 139;TYR 193;LYS 197
1wmaASER 139;TYR 193;LYS 197
2pfgASER 139;TYR 193;LYS 197
3bhiASER 139;TYR 193;LYS 197
3bhjASER 139;TYR 193;LYS 197
3bhmASER 139;TYR 193;LYS 197

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]p.42
[12]p.559-560

references
[1]
PubMed ID3511844
JournalArch Biochem Biophys
Year1986
Volume244
Pages238-47
AuthorsHara A, Nakayama T, Deyashiki Y, Kariya K, Sawada H
TitleCarbonyl reductase of dog liver: purification, properties, and kinetic mechanism.
[2]
PubMed ID2388711
JournalNeurochem Res
Year1990
Volume15
Pages385-92
AuthorsHayashi H, Fujii Y, Watanabe K, Hayaishi O
TitleEnzymatic formation of prostaglandin F2 alpha in human brain.
[3]
PubMed ID1449827
JournalEicosanoids
Year1992
Volume5 Suppl
PagesS37-8
AuthorsSchieber A, Ghisla S
TitleProstaglandin 9-ketoreductase from pig and human kidney: purification, properties and identity with human carbonyl reductase.
[4]
PubMed ID1576998
JournalEur J Biochem
Year1992
Volume205
Pages1155-62
AuthorsKlein J, Thomas H, Post K, Worner W, Oesch F
TitleDihydrodiol dehydrogenase activities of rabbit liver are associated with hydroxysteroid dehydrogenases and aldo-keto reductases.
[5]
PubMed ID1597188
JournalEur J Biochem
Year1992
Volume206
Pages491-502
AuthorsSchieber A, Frank RW, Ghisla S
TitlePurification and properties of prostaglandin 9-ketoreductase from pig and human kidney. Identity with human carbonyl reductase.
[6]
PubMed ID8421682
JournalProc Natl Acad Sci U S A
Year1993
Volume90
Pages502-6
AuthorsKrook M, Ghosh D, Stromberg R, Carlquist M, Jornvall H
TitleCarboxyethyllysine in a protein: native carbonyl reductase/NADP(+)-dependent prostaglandin dehydrogenase.
[7]
PubMed ID7990149
JournalJ Mol Biol
Year1994
Volume244
Pages659-64
AuthorsBohren KM, Wermuth B, Harrison D, Ringe D, Petsko GA, Gabbay KH
TitleExpression, crystallization and preliminary crystallographic analysis of human carbonyl reductase.
[8]
PubMed ID7981120
JournalJ Steroid Biochem Mol Biol
Year1994
Volume51
Pages125-30
AuthorsKrozowski Z
TitleThe short-chain alcohol dehydrogenase superfamily: variations on a common theme.
[9]
PubMed ID8889808
JournalJ Biochem (Tokyo)
Year1996
Volume120
Pages257-63
AuthorsNakanishi M, Kakumoto M, Matsuura K, Deyashiki Y, Tanaka N, Nonaka T, Mitsui Y, Hara A
TitleInvolvement of two basic residues (Lys-17 and Arg-39) of mouse lung carbonyl reductase in NADP(H)-binding and fatty acid activation: site-directed mutagenesis and kinetic analyses.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NADPH.
PubMed ID8805511
JournalStructure
Year1996
Volume4
Pages33-45
AuthorsTanaka N, Nonaka T, Nakanishi M, Deyashiki Y, Hara A, Mitsui Y
TitleCrystal structure of the ternary complex of mouse lung carbonyl reductase at 1.8 A resolution: the structural origin of coenzyme specificity in the short-chain dehydrogenase/reductase family.
Related PDB1cyd
Related UniProtKBP08074
[11]
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.
[12]
PubMed ID9059662
JournalAdv Exp Med Biol
Year1997
Volume414
Pages555-61
AuthorsNakanishi M, Kaibe H, Matsuura K, Kakumoto M, Tanaka N, Nonaka T, Mitsui Y, Hara A
TitleSite-directed mutagenesis of residues in coenzyme-binding domain and active site of mouse lung carbonyl reductase.
[13]
CommentsMUTAGENESIS OF THR-38, AND COENZYME SPECIFICITY.
PubMed ID8999926
JournalJ Biol Chem
Year1997
Volume272
Pages2218-22
AuthorsNakanishi M, Matsuura K, Kaibe H, Tanaka N, Nonaka T, Mitsui Y, Hara A
TitleSwitch of coenzyme specificity of mouse lung carbonyl reductase by substitution of threonine 38 with aspartic acid.
Related UniProtKBP08074
[14]
PubMed ID9729461
JournalBiochem J
Year1998
Volume334
Pages553-7
AuthorsNakajin S, Takase N, Ohno S, Toyoshima S, Baker ME
TitleMutation of tyrosine-194 and lysine-198 in the catalytic site of pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase.
[15]
PubMed ID9880795
JournalJ Biochem (Tokyo)
Year1999
Volume125
Pages41-7
AuthorsImamura Y, Migita T, Otagiri M, Choshi T, Hibino S
TitlePurification and catalytic properties of a tetrameric carbonyl reductase from rabbit heart.
[16]
PubMed ID11279087
JournalJ Biol Chem
Year2001
Volume276
Pages18457-63
AuthorsGhosh D, Sawicki M, Pletnev V, Erman M, Ohno S, Nakajin S, Duax WL
TitlePorcine carbonyl reductase. structural basis for a functional monomer in short chain dehydrogenases/reductases.
Related PDB1hu4,1n5d
[17]
PubMed ID15799708
JournalPLoS Biol
Year2005
Volume3
Pagese128
AuthorsTanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM, Adams CL
TitleAn unbiased cell morphology-based screen for new, biologically active small molecules.
Related PDB1wma
[18]
PubMed ID17912391
JournalOrg Biomol Chem
Year2007
Volume5
Pages3363-7
AuthorsBateman R, Rauh D, Shokat KM
TitleGlutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct.
Related PDB2pfg
[19]
PubMed ID18826943
JournalJ Biol Chem
Year2008
Volume283
Pages35756-62
AuthorsBateman RL, Rauh D, Tavshanjian B, Shokat KM
TitleHuman carbonyl reductase 1 is an S-nitrosoglutathione reductase.
Related PDB3bhi,3bhj,3bhm

comments
Although this enzyme has three E.C. numbers, it is homologous to carbonyl reductase (1.1.1.184) (S00331 in EzCatDB).
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 NADP+ molecule, seems to be similar to those of the homologous enzymes.
This enzyme seems to catalyze the reduction of a variety of carbonyl compounds.
According to the literature [19], this enzyme binds glutathione near the active site. However, its reaction mechanism should be elucidated more clearly.

createdupdated
2005-01-242011-06-30


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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