Cytochrome oxidase: a perspective

Cytochrome oxidase from beef heart mitochondria is a 2O4 kDa large protein consisting of 13 subunits of which the numbers 1-111 are encoded by the mitochoridrial DNA, while the remaining subunits (IV-VIII) are encoded by the nuclear genome. The protein contains 2 iron heme groups (cytochrome a and cytochrome a3), 2 Cu centres (CUA and CUB) and 1 Zn atom. The heme groups and the CuB centre are located in subunit I, the CuA centre is located on subunit II, whereas subunit Vb contains the Zn site. The spectroscopic features of the oxidase are reviewed in relation to the structure of the metal centres. Cytochrome a occurs in the form of a low-spin bis-imidazole centre; CuA exhibits a high degree of covalency through which a large part of the unpaired electron is delocalized over 1 (or possibly even 2) sulfur ligands. Cytochrome a3 and the Cu9 site form an antiferromagnetically, tightly coupled dinuclear centre, located at the dioxygen reducing side of the protein. The mechanism of electron transfer and the possible proton pumping activity of the enzyme are reviewed in the light of the available structural evidence.