Extended metal environments of cytochrome c oxidase structures

The metals of the cytochrome c oxidase structures of the bovine heart mitochondrion (PDB code 1occ) and of the soil bacterium Paracoccus denitrificans (1arl) include a dicopper center (CuA), magnesium, two proximal hemes, a copper (CuB) atom, and a calcium. The mitochondrial structure also possesses a bound distant zinc ion. The extended environments of the metal sites are analyzed emphasizing residues of the second shell in terms of polarity, hydrophobicity, secondary structure, solvent accessibility, and H-bonding networks. A significant difference in the CuA metal environments concerns D-51 I in 1occ, absent from 1arl. The D-51 I appears to play an important role in the proton pumping pathway. Our analysis uncovers several statistically significant residue clusters, including a cysteine-histidine-tyrosine cluster overlapping the CuA-Mg complex; a histidine-acidic cluster enveloping the environment of Mg, the two hemes, and CuB; and on the protein surface a mixed charge cluster, which may help stabilize the quaternary structure and/or mediate docking to cytochrome c. These clusters may constitute possible pathways for electron transfer, for O2 diffusion, and for H2O movement. Many hydrogen bonding relations along the interface of subunits I and II demarcate this surface as a potential participant in proton pumping.