title: Proton pumping mechanism of bovine heart cytochrome c oxidase.
abstract: X-ray structures of bovine heart cytochrome c oxidase at 1.8/1.9 A resolution in the oxidized/reduced states exhibit a redox coupled conformational change of an aspartate located near the intermembrane surface of the enzyme. The alteration of the microenvironment of the carboxyl group of this aspartate residue indicates the occurrence of deprotonation upon reduction of the enzyme. The residue is connected with the matrix surface of the enzyme by a hydrogen-bond network that includes heme a via its propionate and formyl groups. These X-ray structures provide evidence that proton pumping occurs through the hydrogen bond network and is driven by the low spin heme. The function of the aspartate is confirmed by mutation of the aspartate to asparagine. Although the amino acid residues of the hydrogen bond network and the structures of the low spin heme peripheral groups are not completely conserved amongst members of the heme-copper terminal oxidase superfamily, the existence of low spin heme and the hydrogen bond network suggests that the low spin heme provides the driving element of the proton-pumping process.
authors.affiliation: Department of Life Science, University of Hyogo, 3-2-1 Kouto, Ako, Hyogo, 678-1297, Japan. yoshi@sci.u-hyogo.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Yoshikawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Muramoto
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinzawa-Itoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Tomitake
authors.initials: T
authors.lastname: Tsukihara
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Shimokata
authors.forename: Yukie
authors.initials: Y
authors.lastname: Katayama
authors.forename: Hideo
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002417:Cattle; D018360:Crystallography, X-Ray; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D017494:Proton Pumps / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017494:Proton Pumps; D003576:Electron Transport Complex IV