Altered spin state equilibrium in the T309V mutant of cytochrome P450 2D6: a spectroscopic and computational study.

ABSTRACT: Cytochrome P450 2D6 (CYP2D6) is one of the most important cytochromes P450 in humans. Resonance Raman data from the T309V mutant of CYP2D6 show that the substitution of the conserved I-helix threonine situated in the enzyme's active site perturbs the heme spin equilibrium in favor of the six-coordinated low-spin species. A mechanistic hypothesis is introduced to explain the experimental observations, and its compatibility with the available structural and spectroscopic data is tested using quantum-mechanical density functional theory calculations on active-site models for both the CYP2D6 wild type and the T309V mutant.

SUBMITTER: Bonifacio A 

PROVIDER: S-EPMC1915625 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature