Microscopic basis for kinetic gating in Cytochrome c oxidase: insights from QM/MM analysis.

ABSTRACT: Understanding the mechanism of vectorial proton pumping in biomolecules requires establishing the microscopic basis for the regulation of both thermodynamic and kinetic features of the relevant proton transfer steps. For the proton pump cytochrome c oxidase, while the regulation of thermodynamic driving force for key proton transfers has been discussed in great detail, the microscopic basis for the control of proton transfer kinetics has been poorly understood. Here we carry out extensive QM/MM free energy simulations to probe the kinetics of relevant proton transfer steps and analyze the effects of local structure and hydration level. We show that protonation of the proton loading site (PLS, taken to be a propionate of heme a₃) requires a concerted process in which a key glutam

SUBMITTER: Goyal P 

PROVIDER: S-EPMC4321873 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature