Cytochrome bo3 and Cytochrome bd terminal oxidases (Cyo/Cyd)

Terminal oxidases CyoC and CydA are essential components of the bacterial respiratory chain, serving as the final enzymes that reduce molecular oxygen to water. Cytochrome bo3 (containing the CyoC subunit) is a heme-copper oxidase that typically functions under high-oxygen conditions and acts as a primary proton pump to generate a transmembrane electrochemical gradient. In contrast, Cytochrome bd (containing the CydA subunit) is a copper-free quinol oxidase with an exceptionally high affinity for oxygen, enabling bacterial survival and pathogenesis under microaerobic, hypoxic, or chemically stressful conditions, such as in the presence of nitric oxide or hydrogen sulfide. These oxidases are critical for the production of ATP via the proton motive force and are found exclusively in prokaryotes, making them highly attractive targets for the development of narrow-spectrum antibiotics. Inhibition of these enzymes, particularly in pathogens like Mycobacterium tuberculosis and Staphylococcus aureus, leads to energy depletion and bacterial death, especially when used in combination with inhibitors of the alternative bc1-aa3 respiratory pathway.

Other names

Cytochrome bo3 ubiquinol oxidaseCytochrome bd ubiquinol oxidaseCytochrome d terminal oxidaseCytochrome o ubiquinol oxidaseCyoABCDE complexCydAB complexQuinol:oxygen oxidoreductase

Inhibition of the quinol-binding site (Q-loop) or disruption of internal electron transfer between heme groups, preventing the reduction of oxygen and the generation of a proton motive force.