Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman spectroscopy

A. Bonifacio, P.H.J. Keizers, J.N.M. Commandeur, N.P.E. Vermeulen, B. Robert, C. Gooijer, G. van der Zwan

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Cytochrome P450 2D6 (CYP2D6) is one of the most important drug-metabolizing enzymes in humans. Resonance Raman data, reported for the first time for CYP2D6, show that the CYP2D6 heme is found to be in a six-coordinated low-spin state in the absence of substrates, and it is perturbed to different extents by bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine (MDMA). Dextromethorphan and MDMA induce in CYP2D6 a significant amount of five-coordinated high-spin heme species and reduce the polarity of its heme-pocket, whereas bufuralol does not. Spectra of the F120A mutant CYP2D6 suggest that Phe
Original languageEnglish
Pages (from-to)772-9
JournalBiochemical and Biophysical Research Communications
Volume343
Issue number3
DOIs
Publication statusPublished - 2006

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