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 aa 3 terminal oxidases of the 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 aa 3 oxidase, which decreases by more than 200 mV the E m of heme a , inhibits proton pumping. Mutational aminoacid replacement in proton channels, at the negative (N) side of membrane-inserted prokaryotic aa 3 oxidases, as well as Zn 2 + binding at this site in the bovine oxidase, uncouples proton pumping. This effect appears to result from alteration of the structural/functional device, closer to the positive, opposite (P) surface, which separates pumped protons from those consumed in the reduction of O 2 to 2 H 2 O. This article is part of a Special Issue entitled: Respiratory Oxidases.