Explaining leak states in the proton pump of heme-copper oxidases observed in single-molecule experiments

Abstract

Heme-copper oxidases couple the exergonic oxygen reduction with the endergonic proton translocation. Redox-linked structural changes have been localized in deeply buried regions of the protein, near the low-potential heme. How these movements can modulate distant gating events along the intramolecular proton path, where the entry (exit) of pumped proton occurs, is a major concern for the proton pump models. Generally, these models associate, more or less directly, all translocation events with redox transitions. Although they can account for many phenomenological aspects of the pump, evidences from single-molecules experiments about leak states of the pump represent a formidable challenge. Disconnecting the redox-linked pKa shifts of the proton loading site from the external barriers, we obtain a simple stochastic mechanism which behaves similarly to the real enzyme, able to reverse the flow of the proton transfer.