title: Gating and regulation of the cytochrome c oxidase proton pump.
abstract: As a consumer of 95% of the oxygen we breathe, cytochrome c oxidase plays a major role in the energy balance of the cell. Regulation of its oxygen reduction and proton pumping activity is therefore critical to physiological function in health and disease. The location and structure of pathways for protons that are required to support cytochrome c oxidase activity are still under debate, with respect to their requirements for key residues and fixed waters, and how they are gated to prevent (or allow) proton backflow. Recent high resolution structures of bacterial and mammalian forms reveal conserved lipid and steroid binding sites as well as redox-linked conformational changes that provide new insights into potential regulatory ligands and gating modes. Mechanistic interpretation of these findings and their significance for understanding energy regulation is discussed.
authors.affiliation: Michigan State University, East Lansing, MI, USA. fergus20@msu.edu
authors.forename: Shelagh
authors.initials: S
authors.lastname: Ferguson-Miller
authors.forename: Carrie
authors.initials: C
authors.lastname: Hiser
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport; D018360:Crystallography, X-Ray; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011522:Protons; D012242:Rhodobacter sphaeroides / Q000201:enzymology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011522:Protons; D003576:Electron Transport Complex IV