Cytochrome c oxidase CcO is a crucial enzyme in the electron transport chain of mitochondria, responsible for the reduction of molecular oxygen to water. This enzyme contains two copper centers, Cu_A and Cu_B, which play essential roles in the catalytic process.Cu_A is a binuclear copper center, consisting of two copper ions Cu1 and Cu2 bridged by two cysteine sulfur atoms. Cu_A is responsible for accepting electrons from cytochrome c and transferring them to the heme a prosthetic group. The coordination environment of Cu_A includes two histidine nitrogen atoms, one methionine sulfur atom, and one carbonyl oxygen atom from a nearby peptide backbone. This unique coordination environment facilitates rapid electron transfer between cytochrome c and the heme a prosthetic group.Cu_B, on the other hand, is a mononuclear copper center located near the heme a3 prosthetic group. Cu_B is directly involved in the reduction of molecular oxygen to water. The coordination environment of Cu_B includes three histidine nitrogen atoms, one of which is covalently linked to a nearby tyrosine residue, forming a unique His-Tyr cross-link.The conversion of oxygen and protons into water in the active site of CcO involves a series of redox reactions. The process begins with the transfer of electrons from the reduced cytochrome c to Cu_A, followed by the transfer of electrons to the heme a prosthetic group. The electrons are then transferred to the heme a3-Cu_B binuclear center, where molecular oxygen binds to the heme a3 iron and Cu_B.Upon binding of oxygen, the heme a3 iron and Cu_B are both reduced, leading to the cleavage of the O-O bond and the formation of a peroxide bridge between the heme a3 iron and Cu_B. The subsequent transfer of two more electrons and two protons results in the cleavage of the peroxide bridge and the formation of two water molecules.In summary, copper plays a crucial role in the active site of cytochrome c oxidase by facilitating the transfer of electrons and participating in the reduction of molecular oxygen to water. The unique coordination chemistry of the copper sites, Cu_A and Cu_B, enables efficient electron transfer and catalysis in this essential enzyme.