Thr302 is the site for the covalent modification of human cytochrome P450 2B6 leading to mechanism-based inactivation by tert-butylphenylacetylene.

ABSTRACT: The mechanism-based inactivation of human CYP2B6 by tert-butylphenylacetylene (BPA) in the reconstituted system was investigated. The inactivation of CYP2B6 by BPA is time-, concentration-, and NADPH-dependent and exhibits a K(I) of 2.8 μM, a k(inact) of 0.7 min(-1), and a t(1/2) of 1 min. The partition ratio is ∼5. Unlike CYP2B1 and CYP2B4, in addition to the formation of an apoprotein adduct and a glutathione conjugate, a small heme adduct was observed when CYP2B6 was incubated with BPA. The mass increase of the adducted apoprotein and GSH conjugate is 174 Da, equivalent to the mass of one molecule of BPA plus one oxygen atom. To identify the adducted residue, BPA-inactivated CYP2B6 was digested with trypsin, and the digest was then analyzed by liquid chromatography-tandem mass spectrome

SUBMITTER: Lin HL 

PROVIDER: S-EPMC3226372 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature