title: The influence of subunit III of cytochrome c oxidase on the D pathway, the proton exit pathway and mechanism-based inactivation in subunit I.
abstract: Although subunit III of cytochrome c oxidase is part of the catalytic core of the enzyme, its function has remained enigmatic. Comparison of the wild-type oxidase and forms lacking subunit III shows that the presence of subunit III maintains rapid proton uptake into the D pathway at the pH of the bacterial cytoplasm or mitochondrial matrix, apparently by contributing to the protein environment of D132, the initial proton acceptor of the D pathway. Subunit III also appears to contribute to the conformation of the normal proton exit pathway, allowing this pathway to take up protons from the outer surface of the oxidase in the presence of DeltaPsi and DeltapH. Subunit III prevents turnover-induced inactivation of the oxidase (suicide inactivation) and the subsequent loss of Cu(B) from the active site. This function of subunit III appears partly related to its ability to maintain rapid proton flow to the active site, thereby shortening the lifetime of reactive O(2) reduction intermediates. Analysis of proton pumping by subunit III-depleted oxidase forms leads to the proposal that the trapping of two protons in the D pathway, one on E286 and one on D132, is required for efficient proton pumping.
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA. jhosler@biochem.umsmed.edu
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Hosler
mesh_terms: D003300:Copper / Q000737:chemistry; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D021122:Protein Subunits; D017494:Proton Pumps / Q000737:chemistry / Q000378:metabolism; D018892:Proton-Motive Force; D012242:Rhodobacter sphaeroides / Q000201:enzymology
chemical_list: D021122:Protein Subunits; D017494:Proton Pumps; D003300:Copper; D003576:Electron Transport Complex IV; D010100:Oxygen