Cynomolgus monkey cytochrome P450 2C43: cDNA cloning, heterologous expression, purification and characterization.

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Mitsuda M, Iwasaki M, Asahi S

Cynomolgus monkey cytochrome P450 2C43: cDNA cloning, heterologous expression, purification and characterization.

J Biochem. 2006 May;139(5):865-72. doi: 10.1093/jb/mvj093.

PubMed ID

16751594 [ View in PubMed

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Abstract

The cDNA of cytochrome P450 (CYP) 2C43 was cloned from cynomolgus monkey liver by RT-PCR. The deduced amino acid sequence showed 93% and 91% identity to human CYP2C9 and CYP2C19, respectively. The cDNA was expressed in Escherichia coli and purified by a series of chromatography steps, yielding a specific content of 11.5 nmol P450/mg protein. The substrate specificity of the purified CYP2C43 was examined in a reconstitution system comprising NADPH-P450 reductase, lipid, cytochrome b(5) and CYP2C marker substrates. The purified CYP2C43 showed high activity for testosterone 17-oxidation and progesterone 21-hydroxylation, which were also observed for CYP2C19 but not CYP2C9. In addition, CYP2C43 showed activity for (S)-mephenytoin 4'-hydroxylation, a marker reaction for CYP2C19. With CYP2C9 marker substrates, CYP2C43 exhibited low activity for diclofenac 4'-hydroxylation and no activity for tolbutamide p-methylhydroxylation. Therefore, in terms of substrate specificity, our results indicate that CYP2C43 is similar to CYP2C19, rather than CYP2C9.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Progesterone	Cytochrome P450 2C19	Protein	Humans	Unknown	Substrate Inhibitor	Details