A Modified Arrhenius Approach to Thermodynamically Study Regioselectivity in Cytochrome P450-Catalyzed Substrate Conversion.

ABSTRACT: The regio- (and stereo-)selectivity and specific activity of cytochrome P450s are determined by the accessibility of potential sites of metabolism (SOMs) of the bound substrate relative to the heme, and the activation barrier of the regioselective oxidation reaction(s). The accessibility of potential SOMs depends on the relative binding free energy (ΔΔG_bind ) of the catalytically active substrate-binding poses, and the probability of the substrate to adopt a transition-state geometry. An established experimental method to measure activation energies of enzymatic reactions is the analysis of reaction rate constants at different temperatures and the construction of Arrhenius plots. This is a challenge for multistep P450-catalyzed processes that involve redox partners. We introduce

SUBMITTER: Luirink RA 

PROVIDER: S-EPMC7318578 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature