The K-pathway revisited: a computational study on cytochrome c oxidase.
Cytochrome c oxidase contains two established proton-conducting structures, the D- and K-pathways. The role of the K-pathway appears to be to conduct the first two protons to be used in water formation, which are taken up on reduction of the oxidized enzyme. Previous computational work has suggested that Lys(I)-319 is neutral over a large pH range and in various redox states. We have constructed oxidase models in different redox states using quantum-chemically derived charge parameters for the redox metal centers. The protonation behaviour of titratable sites in the two-subunit enzyme was defined by continuum electrostatics. The calculations reported here show substantial protonation of Lys(I)-319 at neutral pH once the stable X-ray crystallographic water molecule found immediately next to it is treated explicitly. The immediate structure of the Lys(I)-319 environment is independent of redox state, but the pK(a) value of this residue changes with the redox state of the binuclear heme a3/Cu(B) site whenever that change is electrically uncompensated. Lys(I)-319 is also found to interact electrostatically with the conserved residue Glu(II)-62 in subunit II. These results are discussed in relation to the role of the K-pathway in oxidase function.
Tuukkanen
Anne
A
Helsinki Bioenergetics Group, Institute of Biotechnology, University of Helsinki, FIN-00014 University of Helsinki, Helsinki, Finland.
Verkhovsky
Michael I
MI
Laakkonen
Liisa
L
Wikström
Mårten
M
D000818:Animals; D002417:Cattle; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D055672:Static Electricity
D003576:Electron Transport Complex IV