The heme-copper oxidase superfamily shares a Zn2+-binding motif at the entrance to a proton pathway.

Heme-copper oxidases (HCuOs) catalyse the reduction of oxygen, using the liberated free energy to maintain a proton-motive force across the membrane. In the mitochondrial-like A-type HCuOs, binding of heavy metal ions at the surface of the protein inhibits proton transfer. In bacterial C-type oxidases, the entry point to the proton pathway is on an accessory subunit unrelated to any subunit in A-type HCuOs. Despite this, we show here that heavy metal ions such as Zn(2+) inhibit O2-reduction very similarly in C-type as in A-type HCuOs, and furthermore that the binding site shares the same Glu-His motif.