Bacterial metabolic and respiratory enzymes

Bacterial metabolic and respiratory enzymes represent a diverse class of proteins essential for the generation of cellular energy through oxidative phosphorylation and the electron transport chain. This group includes key therapeutic targets such as F-type ATP synthase, Type II NADH dehydrogenase (NDH-2), and various terminal oxidases like the cytochrome bd and bcc-aa3 complexes. These enzymes work coordinately to maintain the proton motive force across the bacterial inner membrane, which is then utilized to drive the synthesis of ATP. Because these bioenergetic pathways are vital for both actively growing and persistent, non-replicating bacteria, they have emerged as high-priority targets for the development of new antibiotics, particularly against recalcitrant pathogens like Mycobacterium tuberculosis. The therapeutic validation of this class is best exemplified by bedaquiline, a diarylquinoline that specifically inhibits the mycobacterial ATP synthase by binding to its c-ring subunit. Other clinical and pre-clinical candidates, such as telacebec, target different components like the cytochrome bcc complex. A major advantage of targeting bacterial respiratory enzymes is the potential for high selectivity, as many bacterial complexes possess structural features or subunits that are absent or significantly different in human mitochondrial counterparts.

Other names

Bacterial bioenergetic enzymesBacterial respiratory chain enzymesBacterial oxidative phosphorylation enzymesBacterial energy metabolism enzymes

Inhibition of F-type ATP synthase c-ring rotation, inhibition of cytochrome bcc complex (QcrB), disruption of proton motive force, and depletion of intracellular ATP levels.