Understanding the essential proton-pumping kinetic gates and decoupling mutations in cytochrome c oxidase

Ruibin Liang, Jessica M. Swanson, Mårten Wikström, Gregory A. Voth

Research output: Contribution to journalArticlepeer-review

Abstract

<jats:p>Cytochrome <jats:italic>c</jats:italic> oxidase (C<jats:italic>c</jats:italic>O) catalyzes the reduction of oxygen to water and uses the released free energy to pump protons against the transmembrane proton gradient. To better understand the proton-pumping mechanism of the wild-type (WT) C<jats:italic>c</jats:italic>O, much attention has been given to the mutation of amino acid residues along the proton translocating D-channel that impair, and sometimes decouple, proton pumping from the chemical catalysis. Although their influence has been clearly demonstrated experimentally, the underlying molecular mechanisms of these mutants remain unknown. In this work, we report multiscale reactive molecular dynamics simulations that characterize the free-energy profiles of explicit proton transport through several important D-channel mutants. Our results elucidate the mechanisms by which proton pumping is impaired, thus revealing key kinetic gating features in C<jats:italic>c</jats:itali
Original languageEnglish
Pages (from-to)5924-5929
JournalProceedings of the National Academy of Sciences of the United States of America
DOIs
StatePublished - Jun 6 2017

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