Computing Redox Potentials of Type-1 Copper Sites Using Combined Quantum Mechanical/Molecular Mechanical Method

Abstract

Type-1 copper proteins, commonly known as blue-copper proteins, represent an important class of oxidoreductases, where the redox active moiety is a copper ion bound in a nitrogen-sulfur donor environment. These proteins act as mediators in electron transport with the copper center shuttling electrons between Cu(II)-Cu(I)oxidation states. One critical element of the redox chemistry of type-1 copper sites is the display of a large variation (between 200 -1000 mV) in the Cu(I/II) redox potential, which translates into a Gibbs free energy difference of 18 kcal/mol. The cause of this large variation is unclear and only speculated to be due to active site hydrophobicity, axial ligation, and outer sphere coordination. In order to gain an insight into the role of the protein matrix on the redox potentials of the copper center, this study used combined quantum mechanical/molecular mechanical simulations. Results of these studies on smaller model systems, as well as type-I proteins, were presented.