The Structure of cbb3 Cytochrome Oxidase Provides Insights into Proton Pumping

The heme-copper oxidases (HCOs) accomplish the key event of aerobic respiration; they couple O-2 reduction and transmembrane proton pumping. To gain new insights into the still enigmatic process, we structurally characterized a C-family HCO-essential for the pathogenicity of many bacteria-that differs from the two other HCO families, A and B, that have been structurally analyzed. The x-ray structure of the C-family cbb(3) oxidase from Pseudomonas stutzeri at 3.2 angstrom resolution shows an electron supply system different from families A and B. Like family-B HCOs, C HCOs have only one pathway, which conducts protons via an alternative tyrosine-histidine cross-link. Structural differences around hemes b and b(3) suggest a different redox-driven proton-pumping mechanism and provide clues to explain the higher activity of family-C HCOs at low oxygen concentrations.