EzCatDB: S00331
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DB codeS00331
RLCP classification9.5010.536200.8010 : Hydride transfer
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
E.C.1.1.1.184

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,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

Q9W3H4P08074Q8WNV7Q9BTZ2O75828
Protein name
Carbonyl reductase {NADPH} 2Dehydrogenase/reductase SDR family member 4Dehydrogenase/reductase SDR family member 4Carbonyl reductase {NADPH} 3carbonyl reductase (NADPH)
aldehyde reductase 1
prostaglandin 9-ketoreductase
xenobiotic ketone reductase
NADPH-dependent carbonyl reductase
ALR3
carbonyl reductase
nonspecific NADPH-dependent carbonyl reductase
aldehyde reductase 1
carbonyl reductase (NADPH)
SynonymsSniffer
EC 1.1.1.184
LD36273p
EC 1.1.1.184
NADPH-dependent carbonyl reductase 2
Lung carbonyl reductase
LCR
Adipocyte protein P27
AP27
EC 1.1.1.184
NADPH-dependent carbonyl reductase/NADP-retinol dehydrogenase
PHCR
CR
Peroxisomal short-chain alcohol dehydrogenase
NADPH-dependent retinol dehydrogenase/reductase
NDRD
EC 1.1.1.184
Short-chain dehydrogenase/reductase family member 4
NADPH-dependent carbonyl reductase/NADP-retinol dehydrogenase
PHCR
CR
Peroxisomal short-chain alcohol dehydrogenase
PSCD
NADPH-dependent retinol dehydrogenase/reductase
NRDR
humNRDR
SCAD-SRL
EC 1.1.1.184
NADPH-dependent carbonyl reductase 3
RefSeqNP_572466.1 (Protein)
NM_132238.3 (DNA/RNA sequence)
NP_031647.1 (Protein)
NM_007621.2 (DNA/RNA sequence)
NP_999184.1 (Protein)
NM_214019.1 (DNA/RNA sequence)
NP_066284.2 (Protein)
NM_021004.2 (DNA/RNA sequence)
NP_001227.1 (Protein)
NM_001236.3 (DNA/RNA sequence)
PfamPF00106 (adh_short)
[Graphical view]
PF00106 (adh_short)
[Graphical view]


PF00106 (adh_short)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00590Arachidonic acid metabolism

UniProtKB:Accession NumberQ9W3H4P08074Q8WNV7Q9BTZ2O75828
Entry nameQ9W3H4_DROMECBR2_MOUSEDHRS4_PIGDHRS4_HUMANCBR3_HUMAN
Activity
R-CHOH-R' + NADP(+) = R-CO-R' + NADPH.R-CHOH-R' + NADP(+) = R-CO-R' + NADPH.R-CHOH-R' + NADP(+) = R-CO-R' + NADPH.R-CHOH-R' + NADP(+) = R-CO-R' + NADPH.
Subunit
Homotetramer.Homotetramer.Homotetramer (By similarity).
Subcellular location
Mitochondrion matrix.Peroxisome.Peroxisome. Note=Isoform 1 is peroxisomal, while isoform 4 is not.Cytoplasm.
Cofactor





Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00005C01450C00080C00006C01612
CompoundNADPHR-CO-R'H+NADP+R-CHOH-R'
Typeamide group,amine group,nucleotidecarbohydrateothersamide group,amine group,nucleotidecarbohydrate
ChEBI16474

15378
18009

PubChem5884

1038
5886

             
1snyAUnboundUnbound Bound:NAPUnbound
1cydAUnboundUnbound Bound:NAPBound:IPA
1cydBUnboundUnbound Bound:NAPBound:IPA
1cydCUnboundUnbound Bound:NAPBound:IPA
1cydDUnboundUnbound Bound:NAPBound:IPA
2zatAUnboundUnbound Bound:NAPUnbound
2zatBUnboundUnbound Bound:NAPUnbound
2zatCUnboundUnbound Bound:NAPUnbound
2zatDUnboundUnbound Bound:NAPUnbound
3o4rAUnboundUnbound Bound:NAPUnbound
3o4rBUnboundUnbound Bound:NAPBound:GOL
3o4rCUnboundUnbound Bound:NAPBound:GOL
3o4rDUnboundUnbound Bound:NAPUnbound
2hrbAUnboundUnbound Bound:NAPUnbound

Active-site residues
resource
Swiss-prot;P08074 & literature [10]
pdbCatalytic residues
         
1snyASER 154;TYR 170;LYS 174
1cydASER 136;TYR 149;LYS 153
1cydBSER 136;TYR 149;LYS 153
1cydCSER 136;TYR 149;LYS 153
1cydDSER 136;TYR 149;LYS 153
2zatASER 151;TYR 164;LYS 168
2zatBSER 151;TYR 164;LYS 168
2zatCSER 151;TYR 164;LYS 168
2zatDSER 151;TYR 164;LYS 168
3o4rASER 169;TYR 182;LYS 186
3o4rBSER 169;TYR 182;LYS 186
3o4rCSER 169;TYR 182;LYS 186
3o4rDSER 169;TYR 182;LYS 186
2hrbASER 140;TYR 194;LYS 198

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]p.42
[12]p.559-560
[17]p.1617
[18]p.392

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 ID15364585
JournalJ Mol Biol
Year2004
Volume342
Pages1613-24
AuthorsSgraja T, Ulschmid J, Becker K, Schneuwly S, Klebe G, Reuter K, Heine A
TitleStructural insights into the neuroprotective-acting carbonyl reductase Sniffer of Drosophila melanogaster.
Related PDB1sny
[18]
PubMed ID18334214
JournalStructure
Year2008
Volume16
Pages388-97
AuthorsTanaka N, Aoki K, Ishikura S, Nagano M, Imamura Y, Hara A, Nakamura KT
TitleMolecular basis for peroxisomal localization of tetrameric carbonyl reductase.
Related PDB2zat
[19]
PubMed ID19056333
JournalArch Biochem Biophys
Year2009
Volume481
Pages183-90
AuthorsEndo S, Maeda S, Matsunaga T, Dhagat U, El-Kabbani O, Tanaka N, Nakamura KT, Tajima K, Hara A
TitleMolecular determinants for the stereospecific reduction of 3-ketosteroids and reactivity towards all-trans-retinal of a short-chain dehydrogenase/reductase (DHRS4).

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.

createdupdated
2005-01-242011-06-30


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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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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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