title: Possible mechanism of proton transfer through peptide groups in the H-pathway of the bovine cytochrome c oxidase.
abstract: The peptide group connecting Tyr440 and Ser441 of the bovine cytochrome c oxidase is involved in a recently proposed proton-transfer path (H-path) where, at variance with other pathways (D- and K-paths), a usual hydrogen-bond network is interrupted, thus making this proton propagation rather unconventional. Our density-functional based molecular dynamics simulations show that, despite this anomaly and provided that a proton can reach a nearby water, a multistep proton-transfer pathway can become a viable pathway for such a reaction: a proton is initially transferred to the carbonyl oxygen of a keto form of the Tyr440-Ser441 peptide group [-CO-NH-], producing an imidic acid [-C(OH)-NH-] as a metastable state; the amide proton of the imidic acid is then transferred, spontaneously to the deprotonated carboxyl group of the Asp51 side chain, leading to the formation of an enol form [-C(OH)=N-] of the Tyr440-Ser441 peptide group. Then a subsequent enol-to-keto tautomerization occurs via a double proton-transfer path realized in the two adjacent Tyr440-Ser441 and Ser441-Asp442 peptide groups. An analysis of this multistep proton-transfer pathway shows that each elementary process occurs through the shortest distance, no permanent conformational changes are induced, thus preserving the X-ray crystal structure, and the reaction path is characterized by a reasonable activation barrier.
authors.affiliation: Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kamiya
authors.forename: Mauro
authors.initials: M
authors.lastname: Boero
authors.forename: Masaru
authors.initials: M
authors.lastname: Tateno
authors.forename: Kenji
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oshiyama
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004583:Electrons; D007536:Isomerism; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011522:Protons
chemical_list: D000596:Amino Acids; D010455:Peptides; D021122:Protein Subunits; D011522:Protons; D003576:Electron Transport Complex IV