STRUCTURES OF METAL SITES OF OXIDIZED BOVINE HEART CYTOCHROME-C-OXIDASE AT 2.8 ANGSTROM

The high resolution three-dimensional x-ray structure of the metal sites of bovine heart cytochrome c oxidase is reported. Cytochrome c oxidase is the largest membrane protein yet crystallized and analyzed at atomic resolution. Electron density distribution of the oxidized bovine cytochrome c oxidase at 2.8 Angstrom resolution indicates a dinuclear copper center with an unexpected structure similar to a [2Fe-2S]-type iron-sulfur center. Previously predicted zinc and magnesium sites have been located, the former bound by a nuclear encoded subunit on the matrix side of the membrane, and the latter situated between heme a(3) and Cu-A, at the interface of subunits I and II. The O-2 binding site contains heme a(3) iron and copper atoms (Cu-B) with an interatomic distance of 4.5 Angstrom; there is no detectable bridging ligand between iron and copper atoms in spite of a strong antiferromagnetic coupling between them. A hydrogen bond is present between a hydroxyl group of the hydroxyfarnesylethyl side chain of heme a(3) and an OH of a tyrosine. The tyrosine phenol plane is immediately adjacent and perpendicular to an imidazole group bonded to Cu-B, suggesting a possible role in intramolecular electron transfer or conformational control, the latter of which could induce the redox-coupled proton pumping. A phenyl group located halfway between a pyrrole plane of the heme a(3) and an imidazole plane liganded to the other home (heme a) could also influence electron transfer or conformational control.