Density-functional calculations of the Cu, Zn superoxide dismutase redox potential: The influence of active site distortion

We have calculated the redox potential for a Cu, Zn superoxide dismutase active-site model. The active site of the enzyme contains a redox active cooper ion coordinated to four histidine residues. The geometry of the active site cooper complex has a characteristic distortion, whose biological significance has been discussed. The computational model contains 47 atoms representing the side chains of the histidine ligands of the copper ion. Thermodynamic parameters were calculated using density-functional methods at the B3LYP level of theory. The energies of the reduced and oxidized forms, allowed us to calculate the reduction potentials for the models. The difference between the reduction potential of a freely optimized model in water (−0.58 V) and a model mimicking the distorted active site geometry (0.84 V) corresponds to +1.42 V. It is expected that the more polar environment (water) stabilizes the oxidized state over the reduced state. However, the distortion around the cooper ion also has a fundamental role in modulating the redox potential, which can be seen by comparing the calculated redox potentials of two active site models, with unconstrained and distorted geometries, both inserted in a proteic environment (0.38 and 0.84 V, respectively). The influence of the active site distortion on the high reduction potential characteristic of this kind of copper proteins, is clearly highlighted by the results, confirming the role of the protein backbone on tuning the reduction potential that is essential for the catalytic efficiency of the enzyme. Furthermore, these preliminary results show a deep contrast with the ones that have been obtained for the Blue Copper Proteins, where it was not found any uncommon structural-function correlation between the geometry of the copper ion and its reduction potential.