Allosteric interactions and proton conducting pathways in proton pumping aa3 oxidases: Heme a as a key coupling element

In this paper allosteric interactions in protonmotive heme aa3 terminal oxidases of respiratory chain are dealt with. The different lines of evidence supporting the key role of H+/e- coupling (redox Bohr effect) at the low spin heme a in the proton pump of the bovine oxidase are summarized. Results are presented showing that the I-R54M mutation in P. denitrificans aa3 oxidase, which decreases by more than 200 mV the Em of heme a, inhibits proton pumping. Mutational aminoacid replacement in proton channels, at the negative (N) side of membrane-inserted prokaryotic aa3 oxidases, as well as Zn2 + binding at this site in the bovine oxidase, uncouple proton pumping. This effect appears to result from alteration of the structural/functional device, closer to the positive, opposite (P) surface, which separate pumped protons from those consumed in the reduction of O2 to 2 H2O. This article is part of a Special Issue entitled: Respiratory Oxidases