title: Electron transfer pathways in cytochrome c oxidase.
abstract: Mixed quantum mechanical/molecular mechanics calculations were used to explore the electron pathway of the terminal electron transfer enzyme, cytochrome c oxidase. This enzyme catalyzes the reduction of molecular oxygen to water in a multiple step process. Density functional calculations on the three redox centers allowed for the characterization of the electron transfer mechanism, following the sequence Cu(A)→heme a→heme a(3). This process is largely affected by the presence of positive charges, confirming the possibility of a proton coupled electron transfer. An extensive mapping of all residues involved in the electron transfer, between the Cu(A) center (donor) and the O(2) reduction site heme a(3)-Cu(B) (receptor), was obtained by selectively activating/deactivating different quantum regions. The method employed, called QM/MM e-pathway, allowed the identification of key residues along the possible electron transfer paths, consistent with experimental data. In particular, the role of arginines 481 and 482 appears crucial in the Cu(A)→heme a and in the heme a→heme a(3) electron transfer processes. This article is part of a Special Issue entitled: Allosteric cooperativity in respiratory proteins.
authors.affiliation: Barcelona Supercomputing Center, Jordi Girona, Barcelona, Spain.
authors.forename: M Fátima
authors.initials: MF
authors.lastname: Lucas
authors.forename: Denis L
authors.initials: DL
authors.lastname: Rousseau
authors.forename: Victor
authors.initials: V
authors.lastname: Guallar
mesh_terms: D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011522:Protons; D011789:Quantum Theory; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D011522:Protons; D014867:Water; D006418:Heme; D003300:Copper; D001120:Arginine; D003576:Electron Transport Complex IV; D010100:Oxygen