TCB Publications - Abstract

Ivo Hofacker and Klaus Schulten. Oxygen and proton pathways in cytochrome c oxidase. PROTEINS: Structure, Function, and Genetics, 30:100-107, 1998.

HOFA98 Background: Cytochrome c oxidase is a redox-driven proton pump, which couples the reduction of oxygen to water to the translocation of protons across the membrane. The recently solved x-ray structures of cytochrome c oxidase permit molecular dynamics simulations of the underlying transport processes. To eventually establish the proton pump mechanism we investigate the transport of the substrates, oxygen and protons, through the enzyme.
Results: Molecular dynamics simulations of oxygen diffusion through the protein reveal a pathway to the oxygen binding site starting at a hydrophobic cavity near the membrane exposed surface of subunit I, close to the interface to subunit III. A large number of water sites is predicted within the protein. The water molecules form two channels along which protons can enter from the cytoplasmic (matrix) side of the protein and reach the binuclear center.
Conclusions: Oxygen is channeled to the catalytic center of the enzyme along a well defined path. Hydrophobic cavities at the start of the path could serve as reservoirs for oxygen. Water might play an essential role for the transfer of protons in cytochrome c oxidase. A possible pumping mechanism is proposed that involves a shuttling motion of a glutamic acid side chain, which could then transfer a proton to a propionate group of heme $a_{3}$.

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