Conformationally controlled pK-switching in membrane proteins: one more mechanism specific to the enzyme catalysis?

Internal proton displacements in several membrane photosynthetic enzymes are analyzed in relation to general mechanisms of enzymatic catalysis. In the bacterial photosynthetic reaction center (RC) and in bacteriorhodopsin (BR), carboxy residues (Glu-212 in the RC L-subunit and Asp-96 in BR) serve as indispensable intrinsic proton donors. Both carboxyls are protonated prior to the proton-donation step, because their pK values are shifted to >/=12.0 by the interaction with the protein and/or substrate. In both cases, the proton transfer reactions are preceded by conformational changes that, supposedly, let water interact with the carboxyls. These changes switch over the pK values of the carboxyls to </=6.0 and 7.1 in the RC and BR, respectively. The sharp increase in the proton-donating ability of the carboxyls drives the reaction cycles. This kind of catalytic mechanism, where a strong general acid or base emerges, when needed, as a result of a conformational change can be denoted as a conformationally controlled pK-switching. Generally, the ability of enzymes to go between isoenergetic conformations that differ widely in the reactivity of the catalytic group(s) may be of crucial importance to the understanding of enzymatic catalysis. Particularly, the pK-switching concept could help to reconcile the contradictory views on the functional protonation state of the redox-active tyrosine Y(Z) in the oxygen-evolving photosystem II. It is conceivable that Y(Z) switches its pK from approximately 4.5 to >/=10.0 upon the last, rate-limiting step of water oxidation. By turning into a strong base, tyrosine assists then in abstracting a proton from the bound substrate water and helps to drive the dioxygen formation.