F1.Fo ATP Synthase/ATPase: Contemporary View on Unidirectional Catalysis

F-1.F-o-ATP synthases/ATPases (F-1.F-o) are molecular machines that couple either ATP synthesis from ADP and phosphate or ATP hydrolysis to the consumption or production of a transmembrane electrochemical gradient of protons. Currently, in view of the spread of drug-resistant disease-causing strains, there is an increasing interest in F-1.F-o as new targets for antimicrobial drugs, in particular, anti-tuberculosis drugs, and inhibitors of these membrane proteins are being considered in this capacity. However, the specific drug search is hampered by the complex mechanism of regulation of F-1.F-o in bacteria, in particular, in mycobacteria: the enzyme efficiently synthesizes ATP, but is not capable of ATP hydrolysis. In this review, we consider the current state of the problem of unidirectional F-1.F-o catalysis found in a wide range of bacterial F-1.F-o and enzymes from other organisms, the understanding of which will be useful for developing a strategy for the search for new drugs that selectively disrupt the energy production of bacterial cells.

Automated summary

F-1.F-o-ATP synthases/ATPases are molecular machines that are potential targets for antimicrobial drugs, especially anti-tuberculosis drugs. However, the complex regulation mechanism of F-1.F-o in bacteria, particularly mycobacteria, hampers the specific drug search. This review explores the unidirectional catalysis of F-1.F-o and provides insights for developing drugs that selectively disrupt bacterial energy production.