Dewetting transitions coupled to K-channel activation in cytochrome c oxidase.

ABSTRACT: Cytochrome c oxidase (CcO) drives aerobic respiratory chains in all organisms by transducing the free energy from oxygen reduction into an electrochemical proton gradient across a biological membrane. CcO employs the so-called D- and K-channels for proton uptake, but the molecular mechanism for activation of the K-channel has remained elusive for decades. We show here by combining large-scale atomistic molecular simulations with graph-theoretical water network analysis, and hybrid quantum/classical (QM/MM) free energy calculations, that the K-channel is activated by formation of a reactive oxidized intermediate in the binuclear heme a ₃/Cu_B active site. This state induces electrostatic, hydration, and conformational changes that lower the b

SUBMITTER: Supekar S 

PROVIDER: S-EPMC6115622 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature