Active Site Midpoint Potentials in Different Cytochrome c Oxidase Families: A Computational Comparison.
Margareta R A BlombergPublished in: Biochemistry (2019)
Cytochrome c oxidase (C cO) is the terminal enzyme in the respiratory electron transport chain, reducing molecular oxygen to water. The binuclear active site in C cO comprises a high-spin heme associated with a CuB complex and a redox active tyrosine. The electron transport in the respiratory chain is driven by increasing midpoint potentials of the involved cofactors, resulting in a release of free energy, which is stored by coupling the electron transfer to proton translocation across a membrane, building up an electrochemical gradient. In this context, the midpoint potentials of the active site cofactors in the C cOs are of special interest, since they determine the driving forces for the individual oxygen reduction steps and thereby affect the efficiency of the proton pumping. It has been difficult to obtain useful information on some of these midpoint potentials from experiments. However, since each of the reduction steps in the catalytic cycle of oxygen reduction to water corresponds to the formation of an O-H bond, they can be calculated with a reasonably high accuracy using quantum chemical methods. From the calculated O-H bond strengths, the proton-coupled midpoint potentials of the active site cofactors can be estimated. Using models representing the different families of C cO's (A, B, and C), the calculations give midpoint potentials that should be relevant during catalytic turnover. The calculations also suggest possible explanations for why some experimentally measured potentials deviate significantly from the calculated ones, i.e., for CuB in all oxidase families, and for heme b3 in the C family.