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Cavity hydration dynamics in cytochrome c oxidase and functional implications SCIE SCOPUS

Title
Cavity hydration dynamics in cytochrome c oxidase and functional implications
Authors
SON, CHANG YUNYethiraj, ArunCui, Qiang
Date Issued
2017-10-17
Publisher
National Academy of Sciences
Abstract
Cytochrome c oxidase (CcO) is a transmembrane protein that uses the free energy of O-2 reduction to generate the proton concentration gradient across the membrane. The regulation of competitive proton transfer pathways has been established to be essential to the vectorial transport efficiency of CcO, yet the underlying mechanism at the molecular level remains lacking. Recent studies have highlighted the potential importance of hydration-level change in an internal cavity that connects the proton entrance channel, the site of O-2 reduction, and the putative proton exit route. In this work, we use atomistic molecular dynamics simulations to investigate the energetics and timescales associated with the volume fluctuation and hydration-level change in this central cavity. Extensive unrestrained molecular dynamics simulations (accumulatively similar to 4 mu s) and free energy computations for different chemical states of CcO support a model in which the volume and hydration level of the cavity are regulated by the protonation state of a propionate group of heme a3 and, to a lesser degree, the redox state of heme a and protonation state of Glu286. Markov-state model analysis of similar to 2-mu s trajectories suggests that hydration-level change occurs on the timescale of 100-200 ns before the protonloading site is protonated. The computed energetic and kinetic features for the cavity wetting transition suggest that reversible hydration-level change of the cavity can indeed be a key factor that regulates the branching of proton transfer events and therefore contributes to the vectorial efficiency of proton transport.
URI
https://oasis.postech.ac.kr/handle/2014.oak/103377
DOI
10.1073/pnas.1707922114
ISSN
0027-8424
Article Type
Article
Citation
Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 42, page. E8830 - E8836, 2017-10-17
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