Comparative redox and pKa calculations on cytochrome c3 from several Desulfovibrio species using continuum electrostatic methods

A comparative study of the pH-dependent redox mechanisms of several members of the cytochrome c(3) family has been carried out. In a previous work, th e molecular determinants of this dependency (the so-called redox-Bohr effec t) were investigated for one species using continuum electrostatic methods to find groups with a titrating range and strength of interaction compatibl e with a mediating role in the redox-Bohr effect. Here we clarify these asp ects in the light of new and improved pK(a) calculations, our findings supp orting the hypothesis of propionate D from heme I being the main effector i n the pH-dependent modulation of the cytochrome c(3) redox potentials in al l the a molecules studied here. However, the weaker (but significant) role of other titrating groups cannot be excluded, their importance and identity changing with the particular molecule under study. We also calculate the r elative redox potentials of the four heme centers among the selected member s of the c(3) family, using a continuum electrostatic method that takes int o account both solvation and interaction effects. Comparison of the calcula ted values with available data for the microscopic redox potentials was und ertaken, the quality of the agreement being dependent upon the choice of th e dielectric constant for the protein interior. We find that high dielectri c constants give best correlations, while low values result in better magni tudes for the calculated potentials. The possibility that the crystallograp hic calcium ion in c(3) from Desulfovibrio gigas may be present in the solu tion structure was tested, and found to be likely.