A Protonated Water Cluster as a Transient Proton-Loading Site in Cytochrome c Oxidase

• Published in: Angewandte Chemie International Edition Vol. 55; no. 39; pp. 11940 - 11944
• Main Authors: Supekar, Shreyas, Gamiz-Hernandez, Ana P., Kaila, Ville R. I.
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 19-09-2016; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Animals; bioenergetics; Catalytic Domain; Cattle; Clusters; Cytochrome; Cytochrome-c oxidase; Cytochromes; electron transfer; Electron Transport; Electron Transport Complex IV - chemistry; enzymes; molecular dynamics; Molecular Dynamics Simulation; Oxidase; Oxidation-Reduction; Protein kinase A; proton transfer; Protons; Water - chemistry; enzymes; proton transfer; bioenergetics; electron transfer; molecular dynamics
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201603606

Cytochrome c oxidase (CcO) is a redox‐driven proton pump that powers aerobic respiratory chains. We show here by multi‐scale molecular simulations that a protonated water cluster near the active site is likely to serve as the transient proton‐loading site (PLS) that stores a proton during the pumping process. The pKa of this water cluster is sensitive to the redox states of the enzyme, showing distinct similarities to other energy converting proton pumps.
Proton‐coupled electron transfer: Structurally conserved water molecules (see picture) function as a transient proton‐loading site and provide important coupling elements in the proton‐pumping machinery of cytochrome oxidase. Quantum mechanics/molecular mechanics simulations were used to study the biomolecular mechanism.