title: Energy compensation mechanism for charge-separated protonation states in aspartate-histidine amino acid residue pairs.
abstract: The initial stage of proton propagation in the D-path channel of bovine cytochrome c oxidase, consisting of the approach of an H(+) to the entrance of this specific pathway, is inspected via first-principles calculations. Our model, extracted from the X-ray crystallographic structure, includes the amino acid residue pair aspartate (Asp91) and histidine (His503) as protonatable sites. Our calculations show that an additional proton, corresponding to the H(+) uptake by the enzyme from the inner bulk water, is transferred to either Asp91 or His503, leading to the formation of a neutral or a charge-separated protonation state. The relative stability between the two states amounts to a total energy difference of about 5 kcal/mol; this indicates that both Asp91 and His503 are involved in the proton supply to the D-path, playing the role of proton acceptors. The hydrogen-bond environment around Asp91 and His503 has an important influence on both the energetics and the electronic structure of the system; for instance, it compensates the Coulomb-energy cost in the charge-separated protonation state. An energy partitioning analysis shows that the compensatory effect is mainly due to local electrostatic interactions among the charged Asp91 and His503 side chains and the surrounding polar residues. The energy compensation mechanism we found in this work balances the energetics of Asp-His pairs, hence permitting an efficient and selective regulation of the protonatable amino acid residues, where several protonation states are accessible within energy differences of the order of a few H-bonds.
authors.affiliation: Picobiology Institute, Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori, Ako, Hyogo, 678-1297, Japan. kkamiya@sci.u-hyogo.ac.jp
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kamiya
authors.forename: Mauro
authors.initials: M
authors.lastname: Boero
authors.forename: Kenji
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oshiyama
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Shigeta
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry*; D055162:Biocatalysis; D002417:Cattle; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry*; D006860:Hydrogen Bonding; D017434:Protein Structure, Tertiary; D011522:Protons; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D011522:Protons; D001224:Aspartic Acid; D006639:Histidine; D003576:Electron Transport Complex IV