What is the significance of the Tyr radical in cytochrome c oxidase?

Cytochrome c oxidase is a large transmembrane protein complex found in bacteria, archaea, and eukaryotes' mitochondria.It is the last enzyme in the membrane-bound respiratory electron transport chains of cells. Complex IV, also known as cytochrome c oxidase, catalyzes the final step in the mitochondrial electron transport chain and is one of the key regulators of oxidative phosphorylation. Both the nuclear and mitochondrial genomes regulate this enzyme.

The reduction of oxygen to water is catalyzed by cytochrome c oxidase, which is accompanied by pumping four protons across the membrane. In the structure of cytochrome c oxidase, His 276 is cross-linked to Tyr 280, one of the ligands. This puts the Tyr phenolic —OH group close to the heme a3-ligated O₂ so that Tyr 244 can temporarily form a tyrosyl radical (TyrO) and provide the fourth electron. The Tyr phenolic —OH group in cytochrome c oxidase is close enough to the enzyme-bound O2 to form a hydrogen bond, making it a likely H+ donor during the breakage of the O—O bond. Tyr 244 is predicted to have a reduced reduction potential and pK due to the covalent cross-linking, which will facilitate radical production and proton donation.

Hence, Tyr serves as a proton loading site during proton translocation by ejecting a proton upon radical species production.