Electrostatically-driven switches in electron transfer reactions of metalloproteins

MURGIDA, D. H.

Punta del Este

Simposio; 12th International Symposium on Metal Ions in Biology and Medicine; 2013

Natural selection has evolved specialized redox proteins able to perform fast intra- and inter-molecular long range electron transfer (ET) reactions, in the milliseconds time scale and below, in spite of involving nearly null thermodynamic driving forces. Most of these nonadiabatic reactions are well described by the high temperature limit expression of Marcus semiclassical theory. Accordingly, the ET rate is proportional to the square of the electronic coupling matrix element, and to a Frank-Condon exponential term that accounts for the thermal accessibility of such degeneracy. The latter is dominated by the reorganization energy (λ) that accounts for both the energy required to distort the reactants towards the equilibrium configuration of the products and the reorganization of the solvent around the redox center. Here we present a combined spectroscopic, electrochemical and computational study showing that for heme and Cu proteins these parameters are strongly modulated by electrostatic interactions which, in turn, activate either second-sphere ligand conformational switches or enable alternative electronic ground states that provide optimized pathways for electron entry and exit, respectively. Based on these results, we propose that electron transfer chains involved in electron-proton energy transduction are strongly regulated by changes of the membrane potential, as well as by protein-protein interactions, which eventually may lead to a change or gain of function.