Inhibition of membrane-bound cytochrome c oxidase by zinc ions: High-affinity Zn2+-binding site at the P-side of the membrane

In the presence of the uncoupler, external zinc ions inhibit rapidly turnover of cytochrome c oxidase reconstituted in phospholipid vesicles or bound to the membrane of intact mitochondria. The effect is promoted by electron leaks into the oxidase during preincubation with Zn2+. Inhibition of liposome-bound bovine cytochrome oxidase by external Zn2+ titrates with a Ki of 1 ± 0.3 μM. Presumably, the Zn2+-binding group at the positively charged side is not reactive in the oxidized enzyme, but becomes accessible to the cation in some partially reduced state(s) of the oxidase; reduction of CuB is tentatively proposed to be responsible for the effect.