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Information on EC 1.1.1.184 - carbonyl reductase (NADPH) and Organism(s) Homo sapiens and UniProt Accession P16152

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EC Tree
IUBMB Comments
Acts on a wide range of carbonyl compounds, including quinones, aromatic aldehydes, ketoaldehydes, daunorubicin and prostaglandins E and F, reducing them to the corresponding alcohol. Si-specific with respect to NADPH [cf. EC 1.1.1.2 alcohol dehydrogenase (NADP+)].
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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: P16152
Word Map
The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota
The taxonomic range for the selected organisms is: Homo sapiens
Reaction Schemes
Synonyms
15-hydroxyprostaglandin dehydrogenase [NADP+], 2,5-diketo-D-gluconic acid reductase, Adipocyte P27 protein, aldehyde reductase 1, aldehyde reductase I, aldo-keto reductase, ALR3, AP27, carbonyl reductase, carbonyl reductase (NADPH), more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15-hydroxyprostaglandin dehydrogenase [NADP+]
-
-
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Adipocyte P27 protein
-
-
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aldehyde reductase 1
-
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aldehyde reductase I
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-
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-
ALR3
-
-
-
-
AP27
-
-
-
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carbonyl reductase
carbonyl reductase (NADPH)
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-
-
-
carbonyl reductase 1
279258
-
carbonyl reductase 3
247
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CBR
247
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CBR 1
279258
-
CBR 3
283818
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hCBR1
279258
-
LCR
-
-
-
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NADPH-carbonyl reductase
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-
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NADPH-dependent carbonyl reductase
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-
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nonspecific NADPH-dependent carbonyl reductase
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prostaglandin 9-ketoreductase
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-
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Prostaglandin-E2 9-reductase
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reductase, carbonyl
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-
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SDR21C1
279258
-
secondary-alcohol: NADP+-oxidoreductase
247
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xenobiotic carbonyl reductase
247
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xenobiotic ketone reductase
-
-
-
-
additional information
247
the enzyme belongs to the short-chain dehydrogenase/reductase family
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
R-CHOH-R' + NADP+ = R-CO-R' + NADPH + H+
show the reaction diagram
molecular modeling and enzyme-substrate docking studies, reaction mechanism with anthracyclin substrates
-
R-CHOH-R' + NADP+ = R-CO-R' + NADPH + H+
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
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redox reaction
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reduction
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-
SYSTEMATIC NAME
IUBMB Comments
secondary-alcohol:NADP+ oxidoreductase
Acts on a wide range of carbonyl compounds, including quinones, aromatic aldehydes, ketoaldehydes, daunorubicin and prostaglandins E and F, reducing them to the corresponding alcohol. Si-specific with respect to NADPH [cf. EC 1.1.1.2 alcohol dehydrogenase (NADP+)].
CAS REGISTRY NUMBER
COMMENTARY hide
77106-95-7
-
89700-36-7
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89700-37-8
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,2-naphthoquinone + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
-
?
1,4-naphthoquinone + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
-
?
13-deoxydoxorubicin + NADPH + H+
?
show the reaction diagram
an anthracyclin, formation of a 13-hydroxy-anthracyclin
-
-
?
2,3-hexanedione + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
-
?
3-glutathionyl-4-hydroxynonanal + NADP+
3-glutathionyl nonanoic-delta-lactone + NADPH + H+
show the reaction diagram
-
-
oxidation of the hemiacetal form of 3-glutathionyl-4-hydroxynonanal, generating the 3-glutathionyl nonanoic-delta-lactone
-
?
3-glutathionyl-4-hydroxynonanal + NADPH + H+
3-glutathionyl-1,4-dihydroxynonane + NADP+
show the reaction diagram
-
-
-
-
?
3-glutathionyl-hexanal + NADPH + H+
3-glutathionyl-hexan-1-ol + NADP+
show the reaction diagram
-
-
-
-
?
3-glutathionyl-nonanal + NADPH + H+
3-glutathionyl-nonan-1-ol + NADP+
show the reaction diagram
-
-
-
-
?
3-glutathionyl-propanal + NADPH + H+
3-glutathionyl-propan-1-ol + NADP+
show the reaction diagram
-
-
-
-
?
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone + NADPH + H+
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol + NADP+
show the reaction diagram
-
-
-
-
?
4-benzoylpyridine + NADPH + H+
(S)-phenyl(pyridin-4-yl)methanol + NADP+
show the reaction diagram
-
-
-
-
?
4-benzoylpyridine + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NADPH
? + NADP+
show the reaction diagram
-
-
-
?
9,10-phenanthrenequinone + NADPH + H+
? + NADP+
show the reaction diagram
daunorubicin + NADPH + H+
daunorubicinol + NADP+
show the reaction diagram
doxorubicin + NADPH + H+
doxorubicinol + NADP+
show the reaction diagram
isatin + NADPH
? + NADP+
show the reaction diagram
-
-
-
?
isatin + NADPH + H+
3-hydroxy-2-oxoindole + NADP+
show the reaction diagram
-
-
-
-
?
isatin + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
-
?
menadione + NADPH + H+
?
show the reaction diagram
menadione + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
-
?
mitroxantrone + NADPH + H+
?
show the reaction diagram
naphthazarin + NADPH + H+
?
show the reaction diagram
oracin + NADPH + H+
11-dihydrooracin + NADP+
show the reaction diagram
-
-
-
-
?
S-nitrosoglutathione + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
?
2 ferricyanide + NADPH
2 ferrocyanide + NADP+ + H+
show the reaction diagram
-
-
-
-
?
2,3-bornanedione + NADPH
?
show the reaction diagram
-
-
-
-
?
2,3-butanedione + NADPH
?
show the reaction diagram
-
-
-
-
?
2,3-butanedione + NADPH
? + NADP+
show the reaction diagram
-
-
-
?
2-hydroxy-3-butanone + NADPH
2,3-dihydroxybutanol + NADP+
show the reaction diagram
-
-
-
?
2-nitrobenzaldehyde + NADPH
2-nitrobenzyl alcohol + NADP+
show the reaction diagram
-
-
-
-
?
3-glutathionyl-4-hydroxynonanal + NADPH + H+
3-glutathionyl-1,4-dihydroxynonane + NADP+
show the reaction diagram
-
-
-
-
?
4-benzoylpyridine + NADPH
(S)-alpha-phenyl-4-pyridylmethanol + NADP+
show the reaction diagram
4-benzoylpyridine + NADPH
?
show the reaction diagram
-
-
-
-
?
4-carboxybenzaldehyde + NADPH
4-carboxybenzyl alcohol + NADP+
show the reaction diagram
-
-
-
-
?
4-methylnitrosamino-1-(3-pyridyl)-1-butanone + NADPH + H+
4-methylnitrosamino-1-(3-pyridyl)-1-butanol + NADP+
show the reaction diagram
-
i.e. NNK, genotoxic compound from tobacco smoke, isozyme 11beta-HSD1, carbonyl reductase activity, EC 1.1.1.184
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-
r
4-nitroacetophenone + NADPH
?
show the reaction diagram
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?
4-nitrobenzaldehyde + NADPH
4-nitrobenzyl alcohol + NADP+
show the reaction diagram
4-oxo-2-nonenal + NADPH + H+
? + NADP+
show the reaction diagram
-
9% of the activity with 9,10-phenanthrenequinone
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-
?
4-oxonon-2-enal + NADPH
4-oxononanal + 4-hydroxynon-2-enal + 1-hydroxynon-2-en-4-one + 1,4-dihydroxynon-2-ene + NADP+
show the reaction diagram
-
molecular modeling of substrate binding in the active site
product identification, 4-hydroxynon-2-enal is the major product
-
?
4-oxonon-2-enal + NADPH + H+
1-hydroxynon-2-en-4-one + NADP+
show the reaction diagram
4-oxonon-2-enal + NADPH + H+
4-hydroxynon-2-enal + NADP+
show the reaction diagram
4-oxonon-2-enal + NADPH + H+
4-oxononanal + NADP+
show the reaction diagram
5alpha-androstan-17beta-ol-3-one + NADPH
?
show the reaction diagram
-
-
-
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?
5alpha-androstane-17beta-ol-3-one + NADPH
? + NADP+
show the reaction diagram
-
-
-
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?
5alpha-androstane-3,17-dione + NADPH
?
show the reaction diagram
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only enzyme forms CR2, CR8
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?
5alpha-androstane-3,17-dione + NADPH
? + NADP+
show the reaction diagram
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?
5beta-androstan-17beta-ol-3-one + NADPH
?
show the reaction diagram
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only enzyme forms CR2, CR8
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?
5beta-pregnan-3alpha-ol-20-one + NADPH
? + NADP+
show the reaction diagram
-
-
-
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?
9,10-phenanthrenequinone + NADPH
?
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NADPH
? + NADP+
show the reaction diagram
-
-
-
?
9,10-phenanthrenequinone + NADPH + H+
? + NADP+
show the reaction diagram
alpha-tocopherolquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
bupropion + NADPH + H+
erythrohydrobupropion + NADP+
show the reaction diagram
-
-
in liver cytosol, antidepressant bupropion is reduced to erythrohydrobupropion and threohydrobupropion
-
?
bupropion + NADPH + H+
threohydrobupropion + NADP+
show the reaction diagram
-
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in liver cytosol, antidepressant bupropion is reduced to erythrohydrobupropion and threohydrobupropion
-
?
daunorubicin + NADPH
?
show the reaction diagram
-
-
-
-
?
daunorubicin + NADPH
daunorubicinol + NADP+
show the reaction diagram
doxorubicin + NADPH
doxorubicinol + NADP+
show the reaction diagram
-
-
-
?
duroquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
ethyl acetoacetate + NADPH
? + NADP+
show the reaction diagram
-
-
-
?
glutathione-4-oxonon-2-enal + NADPH
glutathione-4-oxononanal + NADP+
show the reaction diagram
-
conjugate, molecular modeling of substrate binding in the active site
-
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?
glutathione-4-oxonon-2-enal + NADPH + H+
glutathione-4-hydroxynon-2-enal + NADP+
show the reaction diagram
hydrindantin + NADPH
?
show the reaction diagram
-
-
-
-
?
indole 3-acetaldehyde + NADPH
indole-3-ol + NADP+
show the reaction diagram
-
-
-
-
?
isatin + NADPH
? + NADP+
show the reaction diagram
-
-
-
?
isatin + NADPH + H+
3-hydroxy-2-oxoindole + NADP+
show the reaction diagram
-
-
-
-
?
menadione + NADPH
?
show the reaction diagram
menadione + NADPH
? + NADP+
show the reaction diagram
menadione + NADPH + H+
?
show the reaction diagram
-
-
-
-
?
menadione + NADPH + H+
? + NADP+
show the reaction diagram
-
48% of the activity with 9,10-phenanthrenequinone
-
-
?
methylglyoxal + NADPH
?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
oracin + NADPH + H+
dihydrooracin + NADP+
show the reaction diagram
phenylglyoxal + NADPH
?
show the reaction diagram
-
-
-
-
?
prostaglandin A-GSH + NADPH
?
show the reaction diagram
-
-
-
-
?
prostaglandin B2 + NADPH
?
show the reaction diagram
-
-
-
-
?
prostaglandin E2 + NADPH
?
show the reaction diagram
prostaglandin E2 + NADPH
prostaglandin F2alpha + NADP+
show the reaction diagram
-
-
-
-
-
pyridine-4-carboxaldehyde + NADPH
?
show the reaction diagram
-
-
-
-
?
S-nitrosoglutathione + NADPH + H+
? + NADP+
show the reaction diagram
no substrate for wild-type, but substrate for mutants D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P, P230W/D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P, and Q142M/C143S/P230W/D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P/H270S
-
-
?
ubiquinone-1 + NADPH
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
daunorubicin + NADPH + H+
daunorubicinol + NADP+
show the reaction diagram
P16152
reduction of the anthracycline C13 carbonyl results in a 13-hydroxy metabolite that elicits potent cardiotoxic effects while possessing significantly reduced anticancer properties
-
-
?
doxorubicin + NADPH + H+
doxorubicinol + NADP+
show the reaction diagram
P16152
reduction of the anthracycline C13 carbonyl results in a 13-hydroxy metabolite that elicits potent cardiotoxic effects while possessing significantly reduced anticancer properties
-
-
?
menadione + NADPH + H+
?
show the reaction diagram
P16152
reduction of the anthracycline C13 carbonyl results in a 13-hydroxy metabolite that elicits potent cardiotoxic effects while possessing significantly reduced anticancer properties
-
-
?
mitroxantrone + NADPH + H+
?
show the reaction diagram
P16152
reduction of the anthracycline C13 carbonyl results in a 13-hydroxy metabolite that elicits potent cardiotoxic effects while possessing significantly reduced anticancer properties
-
-
?
naphthazarin + NADPH + H+
?
show the reaction diagram
P16152
reduction of the anthracycline C13 carbonyl results in a 13-hydroxy metabolite that elicits potent cardiotoxic effects while possessing significantly reduced anticancer properties
-
-
?
4-methylnitrosamino-1-(3-pyridyl)-1-butanone + NADPH + H+
4-methylnitrosamino-1-(3-pyridyl)-1-butanol + NADP+
show the reaction diagram
-
i.e. NNK, genotoxic compound from tobacco smoke, isozyme 11beta-HSD1, carbonyl reductase activity, EC 1.1.1.184
-
-
r
4-oxonon-2-enal + NADPH + H+
1-hydroxynon-2-en-4-one + NADP+
show the reaction diagram
-
metabolic inactivation of the lipid peroxidation product, pathway overview
-
-
?
4-oxonon-2-enal + NADPH + H+
4-hydroxynon-2-enal + NADP+
show the reaction diagram
-
metabolic inactivation of the lipid peroxidation product, pathway overview
-
-
?
4-oxonon-2-enal + NADPH + H+
4-oxononanal + NADP+
show the reaction diagram
-
metabolic inactivation of the lipid peroxidation product, pathway overview
-
-
?
glutathione-4-oxonon-2-enal + NADPH + H+
glutathione-4-hydroxynon-2-enal + NADP+
show the reaction diagram
-
metabolic inactivation of the lipid peroxidation product, pathway overview
-
-
?
oracin + NADPH + H+
dihydrooracin + NADP+
show the reaction diagram
-
a cytostatic drug, isozyme 11beta-HSD1, carbonyl reductase activity, EC 1.1.1.184, stereochemical ratio of 3:1 for R:S enantiomers of the pro-chiral carbonyl centre of oracin, inactivation of the anti-cancer drug
-
-
r
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
NADH
with NADH, about 45% of the activity with NADPH
NADP+
NADPH
additional information
-
no cofactor: NADH
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
-
detected in enzyme by atomic absorption spectroscopy
Magnesium
-
detected in enzyme by atomic absorption spectroscopy
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3',4',7-tris[O-(2-hydroxyethyl)]rutin
-
-
4-amino-1-tert-butyl-3-(2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidine
-
-
7-monohydroxyethylrutoside
-
inhibits the activity of CBR1 V88 and CBR1 I88 in a concentration-dependent manner. It acts as a competitive CBR1 inhibitor when using daunorubicin as a substrate and acts as an uncompetitive CBR1 inhibitor for the small quinone substrate menadione. It inhibits the binding of NADPH in an uncompetitive manner for both substrates
quercetin
-
-
rutin
-
-
S-nitrosoglutathione
(2E)-1-(2,4-dihydroxyphenyl)-3-(2',4',6-trihydroxy-5'-[(2E)-3-(4-hydroxyphenyl)prop-2-enoyl]biphenyl-3-yl)prop-2-en-1-one
-
14,16-dihydroxy-3,8-dimethyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
-
zearalenone analogue
18beta-glycyrrhetinic acid
-
inhibits the reduction of bupropion in liver microsomes
2,3-Butanedione
-
irreversible inactivation
3-(2-(2,4-dihydroxyphenyl)-1-[hydroxy(4-hydroxyphenyl)methyl]-2-oxoethyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
-
3-[2,3-dihydroxy-4-methoxy-5-(3-methylbut-2-en-1-yl)phenyl]-5,7-dihydroxy-4H-chromen-4-one
-
3-[2-(2,4-dihydroxyphenyl)-1-(4-hydroxybenzyl)-2-oxoethyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
-
4-Oxo-4H-benzopyran-2-carboxylic acid
-
-
4-oxonon-2-enal
-
the substrate is also a mechanism-based inhibitor of the enzyme resulting in 50% inactivation of the enzyme-NADPH complex, presence of cofactor is required for inhibition
7-O-beta-D-glucopyranos2-ulosyl-quercetin
-
Biochanin A
-
-
chlorogenic acid
-
-
chlorpromazine
-
-
chrysin
-
-
Cibacron blue
-
3G-A
D-catechin
-
-
dicoumarol
-
-
Ethacrynic acid
-
-
flavonoids
-
-
glycyrrhetinic acid
-
inhibits both 11beta-hydroxysteroid dehydrogenase and carbonyl reductase activities of the enzyme potently
indomethacin
-
-
iodoacetate
-
-
menadione
-
inhibits the reduction of bupropion in liver cytosol
NADP+
-
-
naringenin
-
-
p-hydroxymercuribenzoate
-
-
Phenylglyoxal
-
irreversible inactivation
quercetin
-
-
quercitrin
-
-
Retin
-
-
-
Tetramethyleneglutaric acid
-
-
triclosan
-
-
wedelolactone
-
-
additional information
-
no inhibition by NADP+
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
CR expression is upregulated in brains suffering from Alzheimers disease
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.07 - 0.117
1,2-naphthoquinone
0.0073 - 0.032
1,4-Naphthoquinone
0.06 - 0.159
2,3-Hexanedione
0.0238
3-glutathionyl-hexanal
-
pH 8.4, 25C
0.0065
3-glutathionyl-nonanal
-
pH 8.4, 25C
0.0207
3-glutathionyl-propanal
-
pH 8.4, 25C
5.85 - 7.84
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
0.016 - 0.25
4-benzoylpyridine
0.0128 - 0.0354
9,10-phenanthrenequinone
0.043 - 0.089
daunorubicin
0.132 - 0.335
doxorubicin
0.0008 - 0.017
isatin
0.014 - 0.045
menadione
0.0045
NADPH
-
pH 8.4, 25C
0.034 - 0.096
oracin
0.028 - 0.81
S-nitrosoglutathione
1.8
2,3-Butanedione
-
-
0.8
2-nitrobenzaldehyde
-
-
0.033
3-glutathionyl-4-hydroxynonanal
-
pH 8.4, 37C
0.000000053 - 0.45
4-benzoylpyridine
0.38 - 0.65
4-formylbenzoic acid
-
Km depending on enzyme form
1.3 - 2.5
4-Nitroacetophenone
-
Km depending on enzyme form
0.13 - 2
4-nitrobenzaldehyde
0.345
4-oxonon-2-enal
-
pH 7.4, 37C, recombinant enzyme
0.05 - 0.1
5alpha-androstan-17beta-ol-3-one
0.15
5alpha-androstane-3,17-dione
-
form CR2
0.0043 - 0.078
9,10-phenanthrenequinone
0.3
benzoylpyridine
-
-
0.0852 - 0.3
daunorubicin
0.329
glutathione-4-oxonon-2-enal
-
pH 7.4, 37C, recombinant enzyme
0.0225 - 4
isatin
0.000000067 - 0.07
menadione
0.004 - 0.343
NADPH
1 - 5
Phenylglyoxal
0.14 - 0.21
Prostaglandin B2
-
Km depending on enzyme form
0.45
prostaglandin E1
-
enzyme form CR8
0.1 - 0.32
prostaglandin E2
0.49 - 2
pyridine-4-carboxaldehyde
0.832 - 2.93
S-nitrosoglutathione
0.015 - 0.017
ubiquinone-1
-
Km depending on enzyme form
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.47 - 6.7
1,2-naphthoquinone
0.25 - 0.55
1,4-Naphthoquinone
0.32 - 5.13
2,3-Hexanedione
30.5
3-glutathionyl-hexanal
-
pH 8.4, 25C
30.8
3-glutathionyl-nonanal
-
pH 8.4, 25C
190.8
3-glutathionyl-propanal
-
pH 8.4, 25C
1 - 2.02
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
0.25 - 1.2
4-benzoylpyridine
3.57 - 36.2
9,10-phenanthrenequinone
0.48 - 2.02
daunorubicin
0.0103 - 0.21
doxorubicin
0.17 - 9.77
isatin
0.19 - 0.68
menadione
23.8
NADPH
-
pH 8.4, 25C
0.38 - 1.67
oracin
2.02 - 2.62
S-nitrosoglutathione
6.75
3-glutathionyl-4-hydroxynonanal
-
pH 8.4, 37C
0.009167 - 0.012
4-benzoylpyridine
0.0098
4-nitrobenzaldehyde
pH 6.5, 25C
220
4-oxonon-2-enal
-
pH 7.4, 37C, recombinant enzyme
61 - 91
daunorubicin
8.6
glutathione-4-oxonon-2-enal
-
pH 7.4, 37C, recombinant enzyme
0.0092 - 246
menadione
16.3 - 179
NADPH
18 - 25
prostaglandin E2
5.05 - 20.45
S-nitrosoglutathione
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
50 - 56.7
1,2-naphthoquinone
8.7 - 73.3
1,4-Naphthoquinone
25 - 31.7
2,3-Hexanedione
1281
3-glutathionyl-hexanal
-
pH 8.4, 25C
4615
3-glutathionyl-nonanal
-
pH 8.4, 25C
885
3-glutathionyl-propanal
-
pH 8.4, 25C
0.17 - 0.25
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
4.8 - 15.7
4-benzoylpyridine
113 - 2828
9,10-phenanthrenequinone
11.2 - 18.3
daunorubicin
18.3 - 21.7
isatin
21.7 - 38.3
menadione
5185
NADPH
-
pH 8.4, 25C
11.3 - 12.2
oracin
2.5 - 93.45
S-nitrosoglutathione
1.72 - 24.58
S-nitrosoglutathione
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0105
4-amino-1-tert-butyl-3-(2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidine
-
for doxorubicin metabolism
0.033 - 0.14
7-monohydroxyethylrutoside
0.67
S-nitrosoglutathione
wild-type, pH 7.4, temperature not specified in the publication
0.00004
14,16-dihydroxy-3,8-dimethyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
-
pH 6.9, temperature not specified in the publication
0.00203
Biochanin A
-
pH 6.9, temperature not specified in the publication
0.00011
chrysin
-
pH 6.9, temperature not specified in the publication
0.00343
naringenin
-
pH 6.9, temperature not specified in the publication
0.00052
radiciol
-
pH 6.9, temperature not specified in the publication
0.00006
triclosan
-
pH 6.9, temperature not specified in the publication
0.0006
wedelolactone
-
pH 6.9, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.034 - 0.383
3',4',7-tris[O-(2-hydroxyethyl)]rutin
0.0013
4-amino-1-tert-butyl-3-(2-hydroxyphenyl)pyrazolo[3,4-d]pyrimidine
Homo sapiens
-
for menadione metabolism
0.037 - 0.219
7-monohydroxyethylrutoside
0.014 - 0.043
quercetin
0.0042
(2E)-1-(2,4-dihydroxyphenyl)-3-(2',4',6-trihydroxy-5'-[(2E)-3-(4-hydroxyphenyl)prop-2-enoyl]biphenyl-3-yl)prop-2-en-1-one
Homo sapiens
P16152
pH 7.4, 37C
0.00021
14,16-dihydroxy-3,8-dimethyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
Homo sapiens
-
pH 6.9, temperature not specified in the publication
0.0036
3-(2-(2,4-dihydroxyphenyl)-1-[hydroxy(4-hydroxyphenyl)methyl]-2-oxoethyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Homo sapiens
P16152
pH 7.4, 37C
0.0061
3-[2,3-dihydroxy-4-methoxy-5-(3-methylbut-2-en-1-yl)phenyl]-5,7-dihydroxy-4H-chromen-4-one
Homo sapiens
P16152
pH 7.4, 37C
0.0011
3-[2-(2,4-dihydroxyphenyl)-1-(4-hydroxybenzyl)-2-oxoethyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Homo sapiens
P16152
pH 7.4, 37C
0.008
7-O-beta-D-glucopyranos2-ulosyl-quercetin
Homo sapiens
P16152
pH 7.4, 37C
0.0127
Biochanin A
Homo sapiens
-
pH 6.9, temperature not specified in the publication
0.00067
chrysin
Homo sapiens
-
pH 6.9, temperature not specified in the publication
0.0215
naringenin
Homo sapiens
-
pH 6.9, temperature not specified in the publication
0.0062
quercetin
Homo sapiens
P16152
pH 7.4, 37C
0.0065
quercitrin
Homo sapiens
P16152
pH 7.4, 37C
0.00327
radiciol
Homo sapiens
-
pH 6.9, temperature not specified in the publication
0.0021
rutin
Homo sapiens
P16152
pH 7.4, 37C
0.0004
triclosan
Homo sapiens
-
pH 6.9, temperature not specified in the publication
0.00378
wedelolactone
Homo sapiens
-
pH 6.9, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
161.6
substrate daunorubicin, pH 7.4, 37C
1533
substrate 2,3-butanedione, pH 7.4, 37C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
6
-
menadione, 4-nitrobenzaldehyde, daunorubicin, in sodium phosphate buffer
7.4
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
15% of maximum activity
8
35% of maximum activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
25
-
assay at
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
; low expression of CBR3
Manually annotated by BRENDA team
-
; low expression of CBR3
Manually annotated by BRENDA team
-
; low expression of CBR3
Manually annotated by BRENDA team
-
; low expression of CBR3
Manually annotated by BRENDA team
-
GM10853, GM10845, GM10857, GM10858, GM10860, GM17240, GM16654, GM16688, and GM16689
Manually annotated by BRENDA team
-
; low expression of CBR3
Manually annotated by BRENDA team
-
; low expression of CBR3
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
enzyme expression analysis, 59 different samples
Manually annotated by BRENDA team
; lower expression in prostate and testis than in ovary
Manually annotated by BRENDA team
lower expression in prostate and testis than in ovary
Manually annotated by BRENDA team
additional information
-
overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
CBR1_HUMAN
277
0
30375
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30000
-
1 * 30000, immunoblot analysis
34000
-
Western blot analysis, wild-type and mutants
30000
-
gel filtration, SDS-PAGE, amino acid analysis
31000
-
x * 31000, SDS-PAGE
32000
-
x * 32000, SDS-PAGE
34000
40000
x * 40000, SDS-PAGE, His-tagged protein
67400
-
gel filtration
additional information
-
amino acid composition
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 30000, immunoblot analysis
dimer
-
2 * 34000, SDS-PAGE
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
in presence of S-nitrosoglutathione, S-glutathionylation of cysteines at positions 122, 150, 226, 227 occurs. GSNO treatment of CBR1 results in a 25-fold decrease in kcat with menadione, 4-benzoylpyridine, 2,3-hexanedione, daunorubicin and 1,4-naphthoquinone and an increased kcat for substrates containing a 1,2-diketo group in a ring structure such as 1,2-naphthoquinone, 9,10-phenanthrenequinone, isatin; presence of a disulfide bond between neighboring residues Cys226 and Cys227
CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
in complex with glutathione, in the absence of its substrates or inhibitors. The glutathione molecule contributes to the substrate selectivity and protects the catalytic center of hCBR1 through a switch-like mechanism. Glutathione directly binds with hCBR1 when theres no substrate
-
computational docking experiments for four inhibitors. For flavonoid inhibitors, the flavonoid skeleton is the binding part of the molecule and sugar moieties are pointing outward, giving rise to a stabilizing effect
recombinant protein from Escherichia coli
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C227S
displays a similar kcat, but a 30fold higher Km value for S-nitrosoglutathione, and does not show substrate inhibition
D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P
mutations introduce activity towards S-nitrosoglutathione
P230W
P230W/D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P
mutations introduce activity towards S-nitrosoglutathione
Q142M/C143S/P230W/D236A/K238P/D239K/S240A/I241T/R242K/T243S/V244P/H270S
mutations introduce activity towards S-nitrosoglutathione
V244M
V88I
-
functional genetic polymorphism. Mutation results in CBR1 isoforms with different binding affinities for cofactor NADPH and inhibitor rutin as well as different maximal velocities for reaction with daunorubicin and prostaglandin E2
additional information
residues of CBR3 exchanged to the corresponding amino acids of CBR1. Mutation of nine residues (236-244) in the vicinity of the catalytic center and a proline (P230) in CBR3 to the corresponding residues of CBR1 reveals a much higher kcat/Km value (5.7 micromol/min) towards isatin
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, 0.1 mM NADP+, 1.5 M NaCl, stable for at least 2 weeks
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
by Ni-NTA affinity chromatography
-
recombinant enzyme from Escherichia coli strain BL21(DE3) by anion exchange chromatography
-
3 forms from testis: CR1, CR2, CR3
-
3 molecular forms: CR7, CR8, CR8.5
-
by Ni2+ chelating affinity column chromatography
-
mutants purfied by Ni-affinity chromatography
native enzyme from liver microsomes to homogeneity
-
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
-
recombinant protein
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
CBR1 coding regions excised from a pOTB7 recombinant plasmid and subcloned into pET28a vector. Constructs gave rise to a human CBR1 enzyme with a 6x-His tag separated by an 18-amino acid residue linker on the amino terminus. A factor Xa site inserted at the amino terminus between the linker and CBR1 gene. The pET28a constructs of the CBR1 wild-type and variant enzymes heat-shock transformed into Escherichia coli BL21 (DE3) pLysS-competent cells and expressed under the control of an IPTG-inducible T7 polymerase
-
CBR1 expressed as histidine-tagged protein; CBR3 expressed as histidine-tagged protein
-
expression in Escherichia coli strain BL21(DE3)
-
expression in Escherichia coli
expression in Sacchaormyces cerevisiae
from a liver cDNA library, overexpression in Escherichia coli as His-tagged enzyme
-
from brain
-
isozyme CBR3 V244M, genotyping and polymorphism distribution in 10 different ethnic groups, overview, expression of isozymes CBR V244 and CBR M244 in Escherichia coli strain BL21(DE3)
-
mutants overexpressed in Escherichia coli
overview
-
quantitative enzyme expression analysis in 59 samples of non-small-cell lung cancer, overview
-
wild-type and mutant cloned into the pET-28a vector and expressed in Escherichia coli, BL21(DE3) pLysE cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
-
the single nucleotide polymorphisms in the human CBR1 gene generating the V88I and P131S mutations may prove to be clinically useful genetic biomarkers for guiding anthracycline therapy in cancer patients to minimize adverse effects
diagnostics
-
expression of CBR mRNA is a significant prognostic factor in nonsmall-cell lung cancer and is inversely associated with tumor progression and angiogenesis
medicine
-
antidepressant bupropion is reduced to erythrohydrobupropion and threohydrobupropion in liver. Menadione and 18beta-glycyrrhetinic acid are inhibitory
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wermuth, B.
Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase
J. Biol. Chem.
256
1206-1213
1981
Homo sapiens
Manually annotated by BRENDA team
Bohren, K.M.; von Wartburg, J.P.; Wermuth, B.
Inactivation of carbonyl reductase from human brain by phenylglyoxal and 2,3-butanedione: a comparison with aldehyde reductase and aldose reductase
Biochim. Biophys. Acta
916
185-192
1987
Homo sapiens
Manually annotated by BRENDA team
Bohren, K.M.; von Wartburg, J.P.; Wermuth, B.
Kinetics of carbonyl reductase from human brain
Biochem. J.
244
165-171
1987
Homo sapiens
Manually annotated by BRENDA team
Inazu, N.; Ruepp, B.; Wirth, H.; Wermuth, B.
Carbonyl reductase from human testis: purification and comparison with carbonyl reductase from human brain and rat testis
Biochim. Biophys. Acta
1116
50-56
1992
Homo sapiens
Manually annotated by BRENDA team
Bohren, K.M.; Wermuth, B.; Harrison, D.; Ringe, D.; Petsko, G.A.; Gabbay, K.H.
Expression, crystallization and preliminary crystallographic analysis of human carbonyl reductase
J. Mol. Biol.
244
659-664
1994
Homo sapiens
Manually annotated by BRENDA team
Forrest, G.L.; Gonzalez, B.
Carbonyl reductase
Chem. Biol. Interact.
129
21-40
2000
Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Schieber, A.; Frank, R.W.; Ghisla, S.
Purification and properties of prostaglandin 9-ketoreductase from pig and human kidney. Identity with human carbonyl reductase
Eur. J. Biochem.
206
491-502
1992
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Wermuth, B.; Platts, K.L.; Seidel, A.; Oesch, F.
Carbonyl reductase provides the enzymatic basis of quinone detoxication in man
Biochem. Pharmacol.
35
1277-1282
1986
Homo sapiens
Manually annotated by BRENDA team
Doorn, J.A.; Maser, E.; Blum, A.; Claffey, D.J.; Petersen, D.R.
Human carbonyl reductase catalyzes reduction of 4-oxonon-2-enal
Biochemistry
43
13106-13114
2004
Homo sapiens
Manually annotated by BRENDA team
Maser, E.
Neuroprotective role for carbonyl reductase?
Biochem. Biophys. Res. Commun.
340
1019-1022
2006
Drosophila melanogaster, Homo sapiens
Manually annotated by BRENDA team
Takenaka, K.; Ogawa, E.; Oyanagi, H.; Wada, H.; Tanaka, F.
Carbonyl reductase expression and its clinical significance in non-small-cell lung cancer
Cancer Epidemiol. Biomarkers Prev.
14
1972-1975
2005
Homo sapiens
Manually annotated by BRENDA team
Slupe, A.; Williams, B.; Larson, C.; Lee, L.M.; Primbs, T.; Bruesch, A.J.; Bjorklund, C.; Warner, D.L.; Peloquin, J.; Shadle, S.E.; Gambliel, H.A.; Cusack, B.J.; Olson, R.D.; Charlier, H.A.
Reduction of 13-deoxydoxorubicin and daunorubicinol anthraquinones by human carbonyl reductase
Cardiovasc. Toxicol.
5
365-376
2005
Homo sapiens (P16152)
Manually annotated by BRENDA team
Lakhman, S.S.; Ghosh, D.; Blanco, J.G.
Functional significance of a natural allelic variant of human carbonyl reductase 3 (CBR3)
Drug Metab. Dispos.
33
254-257
2005
Homo sapiens
Manually annotated by BRENDA team
Maser, E.; Wsol, V.; Martin, H.J.
11beta-Hydroxysteroid dehydrogenase type 1: purification from human liver and characterization as carbonyl reductase of xenobiotics
Mol. Cell. Endocrinol.
248
34-37
2006
Homo sapiens
Manually annotated by BRENDA team
Carlquist, M.; Frejd, T.; Gorwa-Grauslund, M.F.
Flavonoids as inhibitors of human carbonyl reductase 1
Chem. Biol. Interact.
174
98-108
2008
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
Gonzalez-Covarrubias, V.; Ghosh, D.; Lakhman, S.S.; Pendyala, L.; Blanco, J.G.
A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity
Drug Metab. Dispos.
35
973-980
2007
Homo sapiens
Manually annotated by BRENDA team
Miura, T.; Nishinaka, T.; Terada, T.
Different functions between human monomeric carbonyl reductase 3 and carbonyl reductase 1
Mol. Cell. Biochem.
315
113-121
2008
Homo sapiens, Homo sapiens (O75828)
Manually annotated by BRENDA team
Miura, T.; Itoh, Y.; Takada, M.; Tsutsui, H.; Yukimura, T.; Nishinaka, T.; Terada, T.
Investigation of the role of the amino acid residue at position 230 for catalysis in monomeric carbonyl reductase 3
Chem. Biol. Interact.
178
211-214
2009
Cricetulus griseus, Homo sapiens, Rattus norvegicus (B2GV72)
Manually annotated by BRENDA team
El-Hawari, Y.; Favia, A.D.; Pilka, E.S.; Kisiela, M.; Oppermann, U.; Martin, H.J.; Maser, E.
Analysis of the substrate-binding site of human carbonyl reductases CBR1 and CBR3 by site-directed mutagenesis
Chem. Biol. Interact.
178
234-241
2009
Homo sapiens (O75828), Homo sapiens (P16152)
Manually annotated by BRENDA team
Kassner, N.; Huse, K.; Martin, H.J.; Goedtel-Armbrust, U.; Metzger, A.; Meineke, I.; Brockmoeller, J.; Klein, K.; Zanger, U.M.; Maser, E.; Wojnowski, L.
Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver
Drug Metab. Dispos.
36
2113-2120
2008
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
Bains, O.S.; Karkling, M.J.; Grigliatti, T.A.; Reid, R.E.; Riggs, K.W.
Two nonsynonymous single nucleotide polymorphisms of human carbonyl reductase 1 demonstrate reduced in vitro metabolism of daunorubicin and doxorubicin
Drug Metab. Dispos.
37
1107-1114
2009
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
Gonzalez-Covarrubias, V.; Zhang, J.; Kalabus, J.L.; Relling, M.V.; Blanco, J.G.
Pharmacogenetics of human carbonyl reductase 1 (CBR1) in livers from black and white donors
Drug Metab. Dispos.
37
400-407
2009
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
Gonzalez-Covarrubias, V.; Kalabus, J.L.; Blanco, J.G.
Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER)
Pharm. Res.
25
1730-1734
2008
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
Zimmermann, T.; Niesen, F.; Pilka, E.; Knapp, S.; Oppermann, U.; Maier, M.
Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone
Bioorg. Med. Chem.
17
530-536
2009
Homo sapiens
Manually annotated by BRENDA team
Staab, C.A.; Hartmanova, T.; El-Hawari, Y.; Ebert, B.; Kisiela, M.; Wsol, V.; Martin, H.J.; Maser, E.
Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3
Chem. Biol. Interact.
191
95-103
2011
Homo sapiens (O75828), Homo sapiens (P16152)
Manually annotated by BRENDA team
Hartmanova, T.; Tambor, V.; Len?o, J.; Staab-Weijnitz, C.A.; Maser, E.; Wsol, V.
S-nitrosoglutathione covalently modifies cysteine residues of human carbonyl reductase 1 and affects its activity
Chem. Biol. Interact.
202
136-145
2013
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
Molnari, J.; Myers, A.
Carbonyl reduction of bupropion in human liver
Xenobiotica
42
550-561
2012
Homo sapiens
Manually annotated by BRENDA team
Moschini, R.; Peroni, E.; Rotondo, R.; Renzone, G.; Melck, D.; Cappiello, M.; Srebot, M.; Napolitano, E.; Motta, A.; Scaloni, A.; Mura, U.; Del-Corso, A.
NADP(+)-dependent dehydrogenase activity of carbonyl reductase on glutathionylhydroxynonanal as a new pathway for hydroxynonenal detoxification
Free Radic. Biol. Med.
83
66-76
2015
Homo sapiens
Manually annotated by BRENDA team
Rotondo, R.; Moschini, R.; Renzone, G.; Tuccinardi, T.; Balestri, F.; Cappiello, M.; Scaloni, A.; Mura, U.; Del-Corso, A.
Human carbonyl reductase 1 as efficient catalyst for the reduction of glutathionylated aldehydes derived from lipid peroxidation
Free Radic. Biol. Med.
99
323-332
2016
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
Liang, Q.; Liu, R.; Du, S.; Ding, Y.
Structural insights on the catalytic site protection of human carbonyl reductase 1 by glutathione
J. Struct. Biol.
192
138-144
2015
Homo sapiens, Homo sapiens (P16152)
Manually annotated by BRENDA team
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