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 (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.