FERRICYTOCHROME c: II. CHAIN FLEXIBILITY AND A POSSIBLE REDUCTION MECHANISM †

ABSTRACT The recent high resolution crystal structure analysis of horse and bonito ferricytochromes c (Dickerson et al., J. Biol. Chem. , 1971, in press) has shown the polypeptide chain path and the positions of all side chains. Evidence from chemical modification of side chains—iodination and nitration of tyrosines, carboxymethylation of methionines, and oxidation of tryptophans—interpreted in the light of the molecular structure, suggests that the left side of the molecule is flexible to a certain extent, and is essential for the reduceability of ferricytochrome c. A free radical mechanism for the reduction of ferricytochrome c , first proposed by M. E. Winfield in 1965 ( J. Mol. Biol. 12, 600), is presented and is shown to be compatible with present structural and chemical information about the left side of the molecule. This mechanism provides different pathways for the electron in reduction and oxidation, and obviates the necessity for the molecule to rotate upon interacting with its reductase and oxidase.