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

Abstract

Cytochrome oxidase activates and reduces O₂ 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 O₂-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 (His²⁴⁰-Tyr²⁴⁴) species is redox active in P formation, which establishes its structure as Fe^IV=O/Cu_B ²⁺-H²⁴⁰-Y²⁴⁴·. Thus, energy transfer from O₂ to the protein moiety is used as a strategy to avoid toxic intermediates and to control energy utilization in subsequent proton-pumping events.