ArticleProceedings of the National Academy of Sciences of the United States of America2016
Multiscale simulations reveal key features of the proton-pumping mechanism in cytochrome c oxidase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 77 citations in OpenAlex.
- Spectroscopic elucidation of an electron-delocalized copper-tyrosine state in heme-copper oxidases reveals its role in proton pumping.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Quinones operate as proton-collecting antennas in energy-transducing membranes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hydration-Controlled Proton Transport in Respiratory Complex I.Journal of the American Chemical Society · 2026Article
- TheProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Solvent Channels and Electric Fields Guide Proton Delivery to the Active Site of Heme Peroxidases.Angewandte Chemie (International ed. in English) · 2025Article
- The three-dimensional structure of a proton-pumping pathway, the H-pathway, is evolutionarily conserved in all three families of cytochromeFrontiers in chemistry · 2025Article
- Hidden water's influence on rhodopsin activation.Biophysical journal · 2024Review
- Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Proton-Coupled Electron Transfer upon Oxidation of Tyrosine in a De Novo Protein: Analysis of Proton Acceptor Candidates.Biochemistry · 2024Article
- Molecular Dynamics Simulation of Complex Reactivity with the Rapid Approach for Proton Transport and Other Reactions (RAPTOR) Software Package.The journal of physical chemistry. B · 2024Article
- Efficient Sampling of Cavity Hydration in Proteins with Nonequilibrium Grand Canonical Monte Carlo and Polarizable Force Fields.Journal of chemical theory and computation · 2024Article
- Transient water wires mediate selective proton transport in designed channel proteins.Nature chemistry · 2023Article
- Protonation-State Dependence of Hydration and Interactions in the Two Proton-Conducting Channels of Cytochrome c Oxidase.International journal of molecular sciences · 2023Article
- Hybrid Quantum Mechanical/Molecular Mechanical Methods For Studying Energy Transduction in Biomolecular Machines.Annual review of biophysics · 2023Review
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Recent progress in experimental studies on the catalytic mechanism of cytochromeFrontiers in chemistry · 2023Review
- Generalized Transition State Theory Treatment of Water-Assisted Proton Transport Processes in Proteins.The journal of physical chemistry. B · 2022Article
- Electric fields control water-gated proton transfer in cytochromeProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Electronic Polarization Is Essential for the Stabilization and Dynamics of Buried Ion Pairs in Staphylococcal Nuclease Mutants.Journal of the American Chemical Society · 2022Article
- Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior.Journal of the American Chemical Society · 2022Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Cytochrome c oxidase (CcO) reduces oxygen to water and uses the released free energy to pump protons across the membrane. We have used multiscale reactive molecular dynamics simulations to explicitly characterize (with free-energy profiles and calculated rates) the internal proton transport events that enable proton pumping during first steps of oxidation of the fully reduced enzyme. Our results show that proton transport from amino acid residue E286 to both the pump loading site (PLS) and to the binuclear center (BNC) are thermodynamically driven by electron transfer from heme a to the BNC, but that the former (i.e., pumping) is kinetically favored whereas the latter (i.e., transfer of the chemical proton) is rate-limiting. The calculated rates agree with experimental measurements. The backflow of the pumped proton from the PLS to E286 and from E286 to the inside of the membrane is prevented by large free-energy barriers for the backflow reactions. Proton transport from E286 to the PLS through the hydrophobic cavity and from D132 to E286 through the D-channel are found to be strongly coupled to dynamical hydration changes in the corresponding pathways and, importantly, vice versa.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.