A single nucleotide polymorphism of CYP2B6 found in japanese enhances catalytic activity by autoactivation

Noritaka Ariyoshi, Masafumi Miyazaki, Kenji Toide, Yu ichi Sawamura, Tetsuya Kamataki

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

A single nucleotide polymorphism (SNP) resulting in a substitution from Gin 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 Vmax 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.

Original languageEnglish
Pages (from-to)1256-1260
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume281
Issue number5
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

Keywords

  • Allosteric effect
  • Autoactivation
  • Cytochrome P450
  • Genetic polymorphism
  • Homotropic cooperativity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A single nucleotide polymorphism of CYP2B6 found in japanese enhances catalytic activity by autoactivation'. Together they form a unique fingerprint.

  • Cite this