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Literature summary for 1.1.1.184 extracted from

  • 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 (2009), Drug Metab. Dispos., 37, 1107-1114.
    View publication on PubMed

Application

Application Comment Organism
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 Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
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 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.018
-
menadione single nucleotide polymorphism V88I mutation Homo sapiens
0.024
-
menadione wild-type Homo sapiens
0.045
-
menadione single nucleotide polymorphism P131S mutation Homo sapiens
0.051
-
daunorubicin wild-type Homo sapiens
0.051
-
daunorubicin single nucleotide polymorphism V88I mutation Homo sapiens
0.089
-
daunorubicin single nucleotide polymorphism P131S mutation Homo sapiens
0.287
-
doxorubicin wild-type Homo sapiens
0.325
-
doxorubicin single nucleotide polymorphism P131S mutation Homo sapiens
0.335
-
doxorubicin single nucleotide polymorphism V88I mutation Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
34000
-
Western blot analysis, wild-type and mutants Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P16152
-
-

Purification (Commentary)

Purification (Comment) Organism
by Ni-NTA affinity chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
daunorubicin + NADPH + H+
-
Homo sapiens daunorubicinol + NADP+
-
?
doxorubicin + NADPH + H+
-
Homo sapiens doxorubicinol + NADP+
-
?
menadione + NADPH + H+
-
Homo sapiens ? + NADP+
-
?
additional information single nucleotide polymorphism V88I and P131S mutations exhibit a 20 to 40% decrease in catalytic efficiency (kcat/Km) compared with that for the wild-type enzyme Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
carbonyl reductase 1
-
Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.15
-
doxorubicin single nucleotide polymorphism V88I mutation Homo sapiens
0.18
-
doxorubicin single nucleotide polymorphism P131S mutation Homo sapiens
0.19
-
menadione single nucleotide polymorphism V88I mutation Homo sapiens
0.21
-
doxorubicin wild-type Homo sapiens
0.3
-
menadione wild-type Homo sapiens
0.33
-
menadione single nucleotide polymorphism P131S mutation Homo sapiens
1.19
-
daunorubicin single nucleotide polymorphism V88I mutation Homo sapiens
1.94
-
daunorubicin wild-type Homo sapiens
2.02
-
daunorubicin single nucleotide polymorphism P131S mutation Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Homo sapiens