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 His18 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 φ, ψ 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 σ-bond, hitherto used for making the paths

A conformational analysis of walker motif A [GXXXXGKT (S)] in nucleotide-binding and other proteins

The sequence GXXXXGKT/S, popularly known as Walker motif A, is widely believed to be the site for binding nucleotides in many proteins. Examination of the crystal structures in the Protein Data Bank showed that about half of the examples having these sequences do not bind or use nucleotides. Data analyses showed 92 different Walker sequences of the variable quartet (XXXX). Ramachandran angles in this segment revealed conformational similarity in the group of 45 proteins, known to bind or utilize nucleotides. The conformations of this segment in other proteins differ widely and it is not known whether they play any role in their functions. A flip of a peptide unit at different locations, with little change in the backbone conformation was noted in nine pairs of these proteins having same Walker sequence. An examination of the immediate neighborhood of the Walker sequence indicates that this region is preceded by a β -strand and followed by an α-helix, resulting in the motif β–W–α, an invariant feature amongst nucleotide-binding proteins