Ab initio study of coupled electron transfer/proton transfer in cytochrome c oxidase

The coupled electron/proton transfer mechanism of cytochrome c oxidase is investigated using ab initio electronic structure theory. We predict the location 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 suggest that a tyrosine residue in close proximity to the active site is deprotonated during the enzymatic cycle. These predictions are consistent with experimental evidence and provide a molecular explanation for both the observed antiferromagnetic coupling of Fe3+ and Cu2+ and the distinction between "fast" and "slow" forms of the oxidized enzyme.