title: Insights into proton translocation in cbb3oxidase from MD simulations.
abstract: Heme-copper oxidases are membrane protein complexes that catalyse the final step of the aerobic respiration, namely the reduction of oxygen to water. The energy released during catalysis is coupled to the active translocation of protons across the membrane, which contributes to the establishment of an electrochemical gradient that is used for ATP synthesis. The distinctive C-type (or cbb3) cytochrome c oxidases, which are mostly present in proteobacteria, exhibit a number of unique structural and functional features, including high catalytic activity at low oxygen concentrations. At the moment, the functioning mechanism of C-type oxidases, in particular the proton transfer/pumping mechanism presumably via a single proton channel, is still poorly understood. In this work we used all-atom molecular dynamics simulations and continuum electrostatics calculations to obtain atomic-level insights into the hydration and dynamics of a cbb3oxidase. We provide the details of the water dynamics and proton transfer pathways for both the "chemical" and "pumped" protons, and show that formation of protonic connections is strongly affected by the protonation state of key residues, namely H243, E323 and H337.
authors.affiliation: Computational Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, United Kingdom; Physics, School of Sciences and Engineering, University of Dundee, Nethergate, Dundee, DD1 4HN, United Kingdom. Electronic address: c.a.c.dossantos@dundee.ac.uk.
authors.forename: Catarina A
authors.initials: CA
authors.lastname: Carvalheda
authors.affiliation: Computational Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, United Kingdom; Physics, School of Sciences and Engineering, University of Dundee, Nethergate, Dundee, DD1 4HN, United Kingdom. Electronic address: a.pisliakov@dundee.ac.uk.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Pisliakov
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D008051:Lipid Bilayers; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D011487:Protein Conformation; D017494:Proton Pumps / Q000378:metabolism*; D011522:Protons; D044223:Pseudomonas stutzeri / Q000201:enzymology* / Q000235:genetics; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship; D014867:Water / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008051:Lipid Bilayers; D017494:Proton Pumps; D011522:Protons; D012997:Solvents; D014867:Water; D000255:Adenosine Triphosphate; C414443:cbb3 oxidase; D003576:Electron Transport Complex IV; D010100:Oxygen
keywords: Cytochrome c oxidase; Membrane protein; Molecular dynamics simulations; Proton pump; Proton transfer; Water dynamics; pK(a) calculations