Electrostatic Regulation of Blue Copper Sites

In the last 50 years, the blue copper proteins became central targets of investigation. Extensive experiments focused on the first- and second-coordination spheres of Cu to probe the effect of local perturbations on its properties. We found that local electric fields, generated by charged residues evolutionarily placed throughout the protein edifice, constitute an additional significant factor regulating blue copper proteins. These fields are not random, but exhibit a highly specific directionality, negative with respect to Cu-S_Cys and Cu-S_Met in the Cu first shell. The field magnitude contributes to fine-tuning of the geometric and electronic properties of Cu sites in individual blue copper proteins. Specifically, the local electric fields evidently control the Cu-S_Met bond distance, Cu(II)-S_Cys bond covalency, and the energies of the frontier molecular orbitals, which, in turn, govern the Cu(II/I) reduction potential and the relative absorption intensities at 450 nm and 600 nm.