OXYGEN AND PROTON PATHWAYS IN CYTOCHROME-C-OXIDASE

Cytochrome c oxidase is a redox-driven proton pump, which couples the reduction of oxygen to water to the translocation of protons across th e membrane, The recently solved x-ray structures of cytochrome c oxida se permit; molecular dynamics simulations of the underlying transport processes, To eventually establish the proton pump mechanism, we inves tigate the transport of the substrates, oxygen and protons, through th e enzyme. Molecular dynamics simulations of oxygen diffusion through t he protein reveal a well-defined pathway to the oxygen-binding site st arting at a hydrophobic cavity near the membrane-exposed surface of su bunit I, close to the interface to subunit III, A large number of wate r sites are predicted within the protein, which could play an essentia l role for the transfer of protons in cytochrome c oxidase, The water molecules form two channels along which protons can enter from tile cy toplasmic (matrix) side of the protein and reach the binuclear center, A possible pumping mechanism is proposed that involves a shuttling mo tion of a glutamic acid. side chain, which could then transfer a proto n to a propionate group of heme alpha(3). (C) 1998 Wiley-Liss, Inc.