Ab initio study of coupled electron transfer/proton transfer in cytochromec oxidase

The coupled electron/proton transfer mechanism of cytochrome c oxidase is i nvestigated using ab initio electronic structure theory. We predict the loc ation and identity of the Fe and Cu ligands in the oxidized (O), partially reduced (E), and fully reduced (R) forms of the enzyme. Our calculations su ggest that a tyrosine residue in close proximity to the active site is depr otonated during the enzymatic cycle. These predictions are consistent with experimental evidence and provide a molecular explanation for both the obse rved antiferromagnetic coupling of Fe3+ and Cu2+ and the distinction betwee n "fast" and "slow" forms of the oxidized enzyme.