Pathways linked by hydrogen bonds with redox-dependent breaks implicated in electron transfer in human cytochrome c protein

Pathways of hydrogen-bond-linked peptide units, polar side chains of the amino acid residues and buried water molecules have been traced in human cytochrome c protein. These connect heme-Fe to the surface through axially coordinated Met80-S and His18-N on the two sides of the heme plate. Oxygen atoms of the heme-propionate side chain and of the internal invariant water molecules form hydrogen bonds in connecting these pathways. With 28 out of the 37 amino acid residues being in the conserved list, these pathways are likely to be common in the highly conserved cytochrome proteins. Selective breaks appear in hydrogen bonds on the Hisl8 side in the oxidized form and on the Met80 side in the reduced form consequent to the accompanying structural changes consistent with a regulatory role. These changes are defined by phi, psi angles of the backbone and dihedral angles of the side chains, between the redox states. The pathways are identical in both the redox forms. They are suitable for intramolecular atom-to-atom electron transfer with hydrogen bond now experimentally found to transfer electrons better than covalent sigma-bond, hitherto used for making the paths.