Cu-To-Cu Electron Tunneling in Copper Monooxygenases

Abstract

The copper enzymes α-hydroxylating monooxygenase (PHM), tyramine β-monooxygenase (TβM) and dopamine β-monooxygenase (DβM) catalyze critical physiological reactions that process hormones and neurotransmitters in higher eukaryotes. In these enzymes, a finely tuned long-range electron-transfer reaction between the enzyme's copper sites is required for catalytic turnover. We conducted extensive electronic structure analysis of PHM, providing understanding of the mechanism of electron tunneling. Our focus has been on the long-range Cu-to-Cu electronic coupling, mediated by protein and by water. Our results indicate that the Tyr79 residue plays an important role in shuttling electrons between the centers. We interpret these results in light of kinetic studies as well as prior theoretical results on related copper oxygenases. Ongoing studies are probing how ligands bound to the catalytic electron acceptor site influence charge transfer kinetics.