Cytochrome c oxidase is a metalloenzyme that plays a crucial role in cellular respiration by catalyzing the reduction of molecular oxygen O2 to water H2O . The active site of cytochrome c oxidase contains two metal ions: a high-spin heme a3 iron Fe and a copper ion CuB .The coordination geometry of the heme a3 iron Fe is octahedral. The iron is coordinated to a histidine imidazole nitrogen, a porphyrin nitrogen, and an oxygen molecule. The oxygen molecule bridges the iron and copper ions.The coordination geometry of the copper ion CuB is square planar. The copper ion is coordinated to three histidine imidazole nitrogens and the bridging oxygen molecule.The oxidation state of the heme a3 iron Fe in the active site varies during the catalytic cycle. It can be in the Fe III or Fe IV state. The copper ion CuB also changes its oxidation state during the catalytic cycle, fluctuating between Cu I and Cu II .In the fully oxidized state, the heme a3 iron Fe is in the Fe IV state, and the copper ion CuB is in the Cu II state. During the four-electron reduction of O2 to H2O, the oxidation states of the metal ions change to facilitate the transfer of electrons and protons, ultimately returning to their initial oxidation states at the end of the catalytic cycle.