Redox-linked hydrogen bond strength changes in cytochrome a: implications for a cytochrome oxidase proton pump

The heme a formyl group of cytochrome a in cytochrome oxidase appears to be involved in a hydrogen-bond interaction with a proton donor associated with the polypeptide backbone [Callahan, P.M., the magnitude of both changes increases as the hydrogen-bond strength increases. Comparison of the model compound data with analogous data for the proteins indicates that the strength of the formyl hydrogen bond in situ increases by 2-2.5 kcal/mol upon reduction of ferric cytochrome a. The selective stabilization of reduced cytochrome a by the stronger hydrogen bond is expected to increase the redox potential of this center; the energy made available as the hydrogen bond strengthens during reduction may be used to drive redox-coupled events in the protein. Thus, the linkage between cytochrome a redox state and chromophore/protein interaction energy provides a mechanism by which electron-transfer events and protein structure are coupled. Two models, which incorporate this linkage into a redox-driven proton pump centered at cytochrome a in cytochrome oxidase, are presented.