CuZn superoxide dismutase geometry optimization, energetics, and redox potential calculations by density functional and electrostatic methods

The structures, energetics, and orbital- and charge-dependent properties of copper zinc superoxide dismutase (CuZnSOD) have been studied using density functional and electrostatic methods. The CuZnSOD was represented with a m odel consisting of copper and zinc sites connected by a bridging histidine ligand. In addition to the bridge, three histidine ligands and one water mo lecule were bonded to the Cu ion in the copper site as first-shell ligands. Two histidine ligands and an aspartate were coordinated to the zinc ion in the zinc site. Full optimization of the model was performed using differen t functionals, both local and nonlocal. Geometrical parameters calculated w ith the nonlocal functionals agree well with the experimental X-ray data. I n our calculated results, the His61 N epsilon-Cu bond in the active site br eaks during the reduction and protonation, consistent with a number of X-ra y structures and with EXAFS and NMR evidence. The reduction potential and p K(a) of the coupled electron/proton reaction catalyzed by CuZnSOD were dete rmined using different models for the extended environment-from an electros tatic representation of continuum solvent, to the full protein/solvent envi ronment using a Poisson-Boltzmann method. The predicted redox potential and pK(a) values determined using the model with the full protein/solvent envi ronment are in excellent agreement with experiment. Inclusion of the full p rotein environment is essential for an accurate description of the redox pr ocess. Although the zinc ion does not play a direct redox role in the dismu tation, its electronic contribution is very important for the catalytic mec hanism.