COMPARISON OF THE PHYSIOLOGICALLY EQUIVALENT PROTEINS CYTOCHROME C(6)AND PLASTOCYANIN ON THE BASIS OF THEIR ELECTROSTATIC POTENTIALS - TRYPTOPHAN-63 IN CYTOCHROME C(6) MAY BE ISOFUNCTIONAL WITH TYROSINE-83 INPLASTOCYANIN

The blue copper protein plastocyanin and the heme protein cytochrome c (6) differ in composition and in structure but perform the same functi on in the photosynthetic electron-transport chain, We compare these tw o proteins on the basis of their electrostatic potentials in order to understand the structural basis of their functional equivalence. In th e first approach, we use a monopole-dipole approximation of the electr ostatic potentials to superimpose the proteins. The resulting alignmen t suggests that Tyr51 in cytochrome c(6) corresponds to Tyr83 in plast ocyanin. But since Tyr51 is not conserved in all known cytochrome c(6) sequences, a physiological role of this residue is questionable. In a more sophisticated approach, we applied the recently-developed FAME ( flexible alignment of molecule ensembles) algorithm, in which molecule s are superimposed by optimizing the similarity of their electrostatic potentials with respect to the relative orientation of the molecules. On the basis of the FAME alignments of plastocyanin and cytochrome c( 6), we analyze the docking and the electron-transfer reactions of thes e two proteins with its physiological reaction partner cytochrome f. W e derive functional analogies for individual amino acids in possible e lectron-transfer paths in the interprotein redox reactions. We identif y two surface patches in cytochrome c(6) that may be involved in elect ron-transfer paths, The hydrophobic patch with the exposed heme edge i n cytochrome c(6) may be equivalent to the hydrophobic patch with His8 7 in plastocyanin, whereas Trp63 in cytochrome c(6) may be equivalent to Tyr83 in plastocyanin. An aromatic amino acid is present at the pos ition of Trp63 in all known cytochrome c(6) sequences. The electronic coupling between the heme and the copper site on the one side and seve ral potentially important amino acid residues on the other is analyzed by the Pathways method. We have proposed recently that Lys65 of cytoc hrome f and Tyr83 of plastocyanin form a cation-pi system, which may b e involved in a two-step mechanism of the electron-transfer reaction b etween these two proteins from higher plants, Now we corroborate this proposal by analyzing available amino acid sequences.