Reaction mechanism of bovine heart cytochrome c oxidase

The 1.9 angstrom resolution X-ray structure of the O(2) reduction site of bovine heart cytochrome c oxidase in the fully reduced state indicates trigonal planar coordination Of CUB by three histidine residues. One of the three histidine residues has a covalent link to a tyrosine residue to ensure retention of the tyrosine at the O(2) reduction site. These moieties facilitate a four electron reduction of O(2), and prevent formation of active oxygen species. The combination of a redox-coupled conformational change of an aspartate residue (Asp51) located near the intermembrane surface of the enzyme molecule and the existence of a hydrogen bond network connecting Asp51 to the matrix surface suggest that the proton-pumping process is mediated at Asp51. Mutation analyses using a gene expression system of the Asp51-containing enzyme subunit yield results in support of the proposal that Asp51 plays a critical role in the proton pumping process. (c) 2006 Elsevier B.V. All rights reserved.