Crystallographic cyanide-probing for cytochrome c oxidase reveals structural bases suggesting that a putative proton transfer H-pathway pumps protons.

Cytochrome c oxidase (CcO) reduces O in the O-reduction site by sequential four-electron donations through the low-potential metal sites (Cu and Fe). Redox-coupled X-ray crystal structural changes have been identified at five distinct sites including Asp, Arg, Glu, the hydroxyfarnesyl ethyl group of heme a, and Ser, respectively. These sites interact with the putative proton-pumping H-pathway.