The chemistry of the CuB site in cytochrome c oxidase and the importance of its unique His-Tyr bond |
| |
Authors: | Ville RI Kaila Mikael P Johansson Liisa Laakkonen |
| |
Institution: | a Helsinki Bioenergetics Group, Programme of Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, P.O. Box 65, FI-00014 Helsinki, Finland b Lundbeck Center for Theoretical Chemistry, Aarhus University, DK-8000 Århus C, Denmark c Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland d Division of Biochemistry, Department of Biological and Environmental Sciences, Faculty of Biosciences, University of Helsinki, FIN-00014, Helsinki, Finland |
| |
Abstract: | The CuB metal center is at the core of the active site of the heme-copper oxidases, comprising a copper atom ligating three histidine residues one of which is covalently bonded to a tyrosine residue. Using quantum chemical methodology, we have studied the CuB site in several redox and ligand states proposed to be intermediates of the catalytic cycle. The importance of the His-Tyr crosslink was investigated by comparing energetics, charge, and spin distributions between systems with and without the crosslink. The His-Tyr bond was shown to decrease the proton affinity and increase the electron affinity of both Tyr-244 and the copper. A previously unnoticed internal electronic equilibrium between the copper atom and the tyrosine was observed, which seems to be coupled to the unique structure of the system. In certain states the copper and Tyr-244 compete for the unpaired electron, the localization of which is determined by the oxygenous ligand of the copper. This electronic equilibrium was found to be sensitive to the presence of a positive charge 10 Å away from the center, simulating the effect of Lys-319 in the K-pathway of proton transfer. The combined results provide an explanation for why the heme-copper oxidases need two pathways of proton uptake, and why the K-pathway is active only in the second half of the reaction cycle. |
| |
Keywords: | pmf proton motive force DFT density functional theory Em 7 mid-point redox potential at pH 7 relative to NHE CcO cytochrome c oxidase cyt c cytochrome c RMSD root mean square deviation wt the model system of the &ldquo wild type&rdquo structure of the CuB site His-Tyr &ldquo mutant&rdquo the insilico mutated model system of the CuB site where the His-Tyr bond has been cut MD molecular dynamics His H &mdash histidine Tyr Y &mdash tyrosine Lys K &mdash lysine Y-OH protonated Tyr Y-O? neutral Tyr-radical Y-O&minus anionic Tyr (tyrosinate) PA proton affinity EA electron affinity HOMO highest occupied molecular orbital LUMO lowest unoccupied molecular orbital |
本文献已被 ScienceDirect 等数据库收录! |
|