Oxygen Activation and Reduction in Respiration: Involvement of Redox-Active Tyrosine 244

Abstract

Cytochrome oxidase activates and reduces O 2 to water to sustain respiration and uses the energy released to drive proton translocation and adenosine 5′-triphosphate synthesis. A key intermediate in this process, P , lies at the junction of the O 2 -reducing and proton-pumping functions. We used radioactive iodide labeling followed by peptide mapping to gain insight into the structure of P . We show that the cross-linked histidine 240–tyrosine 244 (His 240 -Tyr 244 ) species is redox active in P formation, which establishes its structure as Fe IV =O/Cu B 2+ -H 240 -Y 244 ·. Thus, energy transfer from O 2 to the protein moiety is used as a strategy to avoid toxic intermediates and to control energy utilization in subsequent proton-pumping events.