A single nucleotide polymorphism of CYP2b6 found in Japanese enhances catalytic activity by autoactivation.
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Ariyoshi N, Miyazaki M, Toide K, Sawamura Yi, Kamataki T
A single nucleotide polymorphism of CYP2b6 found in Japanese enhances catalytic activity by autoactivation.
Biochem Biophys Res Commun. 2001 Mar;281(5):1256-60.
- PubMed ID
- 11243870 [ View in PubMed]
- Abstract
A single nucleotide polymorphism (SNP) resulting in a substitution from Gln to His was found in exon 4 of the CYP2B6 gene in Japanese. The frequency of the variant allele was found to be 19.9%. The mutant- and the wild-type enzymes were expressed in Escherichia coli, and the effects of the single amino acid substitution on the catalytic activity were examined by investigating the kinetic profiles of 7-ethoxycoumarin O-deethylase activity. The wild-type enzyme showed typical Michaelis-Menten kinetics, while the mutant-type enzyme represented the sigmoidal kinetics with a higher V(max) value compared to that of the wild-type enzyme. Eadie-Hofstee plots further revealed an existence of allosteric effects for the reaction catalyzed by the variant. This is the first evidence demonstrating that only one amino acid substitution, Gln172His, caused by natural SNP enhances the catalytic activity of CYP by obtaining the character of homotropic cooperativity.