Multiscale simulations reveal key features of the proton-pumping mechanism in cytochrome c oxidase.

ABSTRACT: Cytochrome c oxidase (CcO) reduces oxygen to water and uses the released free energy to pump protons across the membrane. We have used multiscale reactive molecular dynamics simulations to explicitly characterize (with free-energy profiles and calculated rates) the internal proton transport events that enable proton pumping during first steps of oxidation of the fully reduced enzyme. Our results show that proton transport from amino acid residue E286 to both the pump loading site (PLS) and to the binuclear center (BNC) are thermodynamically driven by electron transfer from heme a to the BNC, but that the former (i.e., pumping) is kinetically favored whereas the latter (i.e., transfer of the chemical proton) is rate-limiting. The calculated rates agree with experimental measurements. The ba

SUBMITTER: Liang R 

PROVIDER: S-EPMC4941487 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature