Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations

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Sharma , V , Jambrina , P G , Kaukonen , M , Rosta , E & Rich , P R 2017 , ' Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 114 , no. 48 , pp. E10339-E10348 . https://doi.org/10.1073/pnas.1708628114

Title: Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations
Author: Sharma, Vivek; Jambrina, Pablo G.; Kaukonen, Markus; Rosta, Edina; Rich, Peter R.
Contributor: University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
Date: 2017-11-28
Language: eng
Number of pages: 10
Belongs to series: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
URI: http://hdl.handle.net/10138/229665
Abstract: Proton pumping A-type cytochrome c oxidase (CcO) terminates the respiratory chains of mitochondria and many bacteria. Three possible proton transfer pathways (D, K, and H channels) have been identified based on structural, functional, and mutational data. Whereas the D channel provides the route for all pumped protons in bacterial A-type CcOs, studies of bovine mitochondrial CcO have led to suggestions that its H channel instead provides this route. Here, we have studied H-channel function by performing atomistic molecular dynamics simulations on the entire, as well as core, structure of bovine CcO in a lipid-solvent environment. The majority of residues in the H channel do not undergo large conformational fluctuations. Its upper and middle regions have adequate hydration and H-bonding residues to form potential proton-conducting channels, and Asp51 exhibits conformational fluctuations that have been observed crystallographically. In contrast, throughout the simulations, we do not observe transient water networks that could support proton transfer from the N phase toward heme a via neutral His413, regardless of a labile H bond between Ser382 and the hydroxyethylfarnesyl group of heme a. In fact, the region around His413 only became sufficiently hydrated when His413 was fixed in its protonated imidazolium state, but its calculated pK(a) is too low for this to provide the means to create a proton transfer pathway. Our simulations show that the electric dipole moment of residues around heme a changes with the redox state, hence suggesting that the H channel could play a more general role as a dielectric well.
Subject: cell respiration
electron transfer
proton pumping
dielectric well
protein hydration
COUPLED ELECTRON-TRANSFER
ADDITIVE FORCE-FIELD
PROTON PUMP
RHODOBACTER-SPHAEROIDES
PARACOCCUS-DENITRIFICANS
CATALYTIC MECHANISM
MITOCHONDRIAL FORMS
CRYSTAL-STRUCTURE
METAL CENTERS
FREE-ENERGIES
114 Physical sciences
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