Prevention of leak in the proton pump of cytochrome c oxidase

The cytochrome c oxidases (CcO), which are responsible for Most 02 consumption in biology, are also redoxlinked proton pumps that effectively convert the free energy of 02 reduction to an electrochemical proton gradient across mitochondrial and bacterial membranes. Recently, time-resolved measurements have elucidated the sequence of events in proton translocation, and shed light on the underlying molecular mechanisms. One crucial property of the proton pump mechanism has received less attention, viz. how proton leaks are avoided. Here, we will analyse this topic and demonstrate how the key proton-carrying residue Glu-242 (numbering according to the sequence of subunit I of bovine heart CcO) functions as a valve that has the effect of minimising back-leakage of the pumped proton. (c) 2008 Elsevier B.V. All rights reserved.