DB code: S00543

RLCP classification 9.5010.536200.8010 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.1.1.184 1.1.1.189 1.1.1.197
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00551 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
Q28960 Carbonyl reductase [NADPH] 1
EC 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
NP_999238.1 (Protein)
NM_214073.1 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]
P16152 Carbonyl reductase [NADPH] 1
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
NP_001748.1 (Protein)
NM_001757.2 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]

KEGG enzyme name
carbonyl 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 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q28960 CBR1_PIG R-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. Monomer. Cytoplasm (By similarity).
P16152 CBR1_HUMAN 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. Monomer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00590 Arachidonic acid metabolism 1.1.1.184 1.1.1.189

Compound table
Substrates Products Intermediates
KEGG-id C00005 C00080 C01450 C00584 C04654 C00006 C01612 C00639 C04741
E.C. 1.1.1.184
1.1.1.189
1.1.1.197
1.1.1.184
1.1.1.189
1.1.1.197
1.1.1.184
1.1.1.189
1.1.1.197
1.1.1.184
1.1.1.189
1.1.1.197
1.1.1.184
1.1.1.189
1.1.1.197
Compound NADPH H+ R-CO-R' (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate (13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate NADP+ R-CHOH-R' (5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate (13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate
Type amide group,amine group,nucleotide others carbohydrate carbohydrate,fatty acid,lipid carbohydrate,fatty acid,lipid amide group,amine group,nucleotide carbohydrate carbohydrate,fatty acid,lipid carbohydrate,fatty acid,lipid
ChEBI 16474
 16474
 		15378
 15378
 		15551
 15551
 		15548
 15548
 		18009
 18009
 		15553
 15553
 		15544
 15544
PubChem 5884
 5884
 		1038
 1038
 		5280360
 5280360
 		5280710
 5280710
 		5886
 5886
 		5280363
 5280363
 		5280723
 5280723
1hu4A Bound:NDP Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1n5dA Bound:NDP Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1wmaA Bound:NDP Analogue:AB3_307 Unbound Unbound Unbound Unbound Unbound Unbound
2pfgA Unbound Analogue:DDD Unbound Unbound Bound:NAP Unbound Unbound Unbound
3bhiA Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
3bhjA Unbound Analogue:AB3_307 Unbound Unbound Bound:NAP Unbound Unbound Unbound
3bhmA Unbound Analogue:AB3_307 Unbound Unbound Bound:NAP Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [16], [19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1hu4A SER 139;TYR 193;LYS 197
1n5dA SER 139;TYR 193;LYS 197
1wmaA SER 139;TYR 193;LYS 197
2pfgA SER 139;TYR 193;LYS 197
3bhiA SER 139;TYR 193;LYS 197
3bhjA SER 139;TYR 193;LYS 197
3bhmA SER 139;TYR 193;LYS 197

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
p.42
[12]
p.559-560

References
[1]
Resource
Comments
Medline ID
PubMed ID 3511844
Journal Arch Biochem Biophys
Year 1986
Volume 244
Pages 238-47
Authors Hara A, Nakayama T, Deyashiki Y, Kariya K, Sawada H
Title Carbonyl reductase of dog liver: purification, properties, and kinetic mechanism.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2388711
Journal Neurochem Res
Year 1990
Volume 15
Pages 385-92
Authors Hayashi H, Fujii Y, Watanabe K, Hayaishi O
Title Enzymatic formation of prostaglandin F2 alpha in human brain.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1449827
Journal Eicosanoids
Year 1992
Volume 5 Suppl
Pages S37-8
Authors Schieber A, Ghisla S
Title Prostaglandin 9-ketoreductase from pig and human kidney: purification, properties and identity with human carbonyl reductase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1576998
Journal Eur J Biochem
Year 1992
Volume 205
Pages 1155-62
Authors Klein J, Thomas H, Post K, Worner W, Oesch F
Title Dihydrodiol dehydrogenase activities of rabbit liver are associated with hydroxysteroid dehydrogenases and aldo-keto reductases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1597188
Journal Eur J Biochem
Year 1992
Volume 206
Pages 491-502
Authors Schieber A, Frank RW, Ghisla S
Title Purification and properties of prostaglandin 9-ketoreductase from pig and human kidney. Identity with human carbonyl reductase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8421682
Journal Proc Natl Acad Sci U S A
Year 1993
Volume 90
Pages 502-6
Authors Krook M, Ghosh D, Stromberg R, Carlquist M, Jornvall H
Title Carboxyethyllysine in a protein: native carbonyl reductase/NADP(+)-dependent prostaglandin dehydrogenase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 7990149
Journal J Mol Biol
Year 1994
Volume 244
Pages 659-64
Authors Bohren KM, Wermuth B, Harrison D, Ringe D, Petsko GA, Gabbay KH
Title Expression, crystallization and preliminary crystallographic analysis of human carbonyl reductase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 7981120
Journal J Steroid Biochem Mol Biol
Year 1994
Volume 51
Pages 125-30
Authors Krozowski Z
Title The short-chain alcohol dehydrogenase superfamily: variations on a common theme.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8889808
Journal J Biochem (Tokyo)
Year 1996
Volume 120
Pages 257-63
Authors Nakanishi M, Kakumoto M, Matsuura K, Deyashiki Y, Tanaka N, Nonaka T, Mitsui Y, Hara A
Title Involvement 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.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NADPH.
Medline ID
PubMed ID 8805511
Journal Structure
Year 1996
Volume 4
Pages 33-45
Authors Tanaka N, Nonaka T, Nakanishi M, Deyashiki Y, Hara A, Mitsui Y
Title Crystal 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 PDB 1cyd
Related UniProtKB P08074
[11]
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
[12]
Resource
Comments
Medline ID
PubMed ID 9059662
Journal Adv Exp Med Biol
Year 1997
Volume 414
Pages 555-61
Authors Nakanishi M, Kaibe H, Matsuura K, Kakumoto M, Tanaka N, Nonaka T, Mitsui Y, Hara A
Title Site-directed mutagenesis of residues in coenzyme-binding domain and active site of mouse lung carbonyl reductase.
Related PDB
Related UniProtKB
[13]
Resource
Comments MUTAGENESIS OF THR-38, AND COENZYME SPECIFICITY.
Medline ID
PubMed ID 8999926
Journal J Biol Chem
Year 1997
Volume 272
Pages 2218-22
Authors Nakanishi M, Matsuura K, Kaibe H, Tanaka N, Nonaka T, Mitsui Y, Hara A
Title Switch of coenzyme specificity of mouse lung carbonyl reductase by substitution of threonine 38 with aspartic acid.
Related PDB
Related UniProtKB P08074
[14]
Resource
Comments
Medline ID
PubMed ID 9729461
Journal Biochem J
Year 1998
Volume 334
Pages 553-7
Authors Nakajin S, Takase N, Ohno S, Toyoshima S, Baker ME
Title Mutation of tyrosine-194 and lysine-198 in the catalytic site of pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9880795
Journal J Biochem (Tokyo)
Year 1999
Volume 125
Pages 41-7
Authors Imamura Y, Migita T, Otagiri M, Choshi T, Hibino S
Title Purification and catalytic properties of a tetrameric carbonyl reductase from rabbit heart.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11279087
Journal J Biol Chem
Year 2001
Volume 276
Pages 18457-63
Authors Ghosh D, Sawicki M, Pletnev V, Erman M, Ohno S, Nakajin S, Duax WL
Title Porcine carbonyl reductase. structural basis for a functional monomer in short chain dehydrogenases/reductases.
Related PDB 1hu4 1n5d
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 15799708
Journal PLoS Biol
Year 2005
Volume 3
Pages e128
Authors Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM, Adams CL
Title An unbiased cell morphology-based screen for new, biologically active small molecules.
Related PDB 1wma
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 17912391
Journal Org Biomol Chem
Year 2007
Volume 5
Pages 3363-7
Authors Bateman R, Rauh D, Shokat KM
Title Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct.
Related PDB 2pfg
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 18826943
Journal J Biol Chem
Year 2008
Volume 283
Pages 35756-62
Authors Bateman RL, Rauh D, Tavshanjian B, Shokat KM
Title Human carbonyl reductase 1 is an S-nitrosoglutathione reductase.
Related PDB 3bhi 3bhj 3bhm
Related UniProtKB

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 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.
Although this enzyme has three E.C. numbers, it is homologous to carbonyl reductase (1.1.1.184) (S00331 in EzCatDB).

Created Updated
2005-01-24 2011-06-30