ArticleJournal of the American Chemical Society2012
Insights into the mechanism of proton transport in cytochrome c oxidase.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 76 citations in OpenAlex.
- Proton Transfer through a Charged Conduit in Respiratory Complex I: Long-Range Effects and Conformational Gating.Journal of chemical information and modeling · 2025Article
- Current Flow in Nerves and Mitochondria: An Electro-Osmotic Approach.Biomolecules · 2025Review
- Effect of Deuterium Concentration in the Incubation Medium on Intracellular CaBulletin of experimental biology and medicine · 2025Article
- Structural and functional mechanisms of cytochrome c oxidase.Journal of inorganic biochemistry · 2025Review
- Review
- Electric fields control water-gated proton transfer in cytochromeProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Redox-Driven Proton Pumps of the Respiratory Chain.Biophysical journal · 2018Article
- Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase.The Journal of membrane biology · 2018Article
- Cavity hydration dynamics in cytochromeProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mitochondrial determinants of mammalian longevity.Open biology · 2017Article
- Protonation-State-Dependent Communication in Cytochrome c Oxidase.Biophysical journal · 2017Article
- Water exit pathways and proton pumping mechanism in B-type cytochrome c oxidase from molecular dynamics simulations.Biochimica et biophysica acta · 2016Article
- RETRACTED: Protonation State-Dependent Communication in Cytochrome c Oxidase.Biophysical journal · 2016Article
- Multiscale simulations reveal key features of the proton-pumping mechanism in cytochrome c oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- All the O2 Consumed by Thermus thermophilus Cytochrome ba3 Is Delivered to the Active Site through a Long, Open Hydrophobic Tunnel with Entrances within the Lipid Bilayer.Biochemistry · 2016Article
- Computationally Efficient Multiscale Reactive Molecular Dynamics to Describe Amino Acid Deprotonation in Proteins.Journal of chemical theory and computation · 2016Article
- Molecular dynamics analysis to evaluate docking pose prediction.Biophysics and physicobiology · 2016Article
- Theoretical Studies of Interactions between O-Phosphorylated and Standard Amino-Acid Side-Chain Models in Water.The journal of physical chemistry. B · 2015Article
- Microscopic basis for kinetic gating in Cytochrome c oxidase: insights from QM/MM analysis.Chemical science · 2015Article
- Proton translocation in cytochrome c oxidase: insights from proton exchange kinetics and vibrational spectroscopy.Biochimica et biophysica acta · 2015Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Cytochrome c oxidase (CcO), known as complex IV of the electron transport chain, plays several important roles in aerobic cellular respiration. Electrons transferred from cytochrome c to CcO's catalytic site reduce molecular oxygen and produce a water molecule. These electron transfers also drive active proton pumping from the matrix (N-side) to intermembrane region (P-side) in mitochondria; the resultant proton gradient activates ATP synthase to produce ATP from ADP. Although the existence of the coupling between the electron transfer and the proton transport (PT) is established experimentally, its mechanism is not yet fully understood at the molecular level. In this work, it is shown why the reduction of heme a is essential for proton pumping. This is demonstrated via novel reactive molecular dynamics (MD) simulations that can describe the Grotthuss shuttling associated with the PT as well as the dynamic delocalization of the excess proton electronic charge defect. Moreover, the "valve" role of the Glu242 residue (bovine CcO notation) and the gate role of d-propionate of heme a(3) (PRDa3) in the explicit PT are explicitly demonstrated for the first time. These results provide conclusive evidence for the CcO proton transporting mechanism inferred from experiments, while deepening the molecular level understanding of the CcO proton switch.
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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.