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

• Published in: International journal of molecular sciences Vol. 24; no. 6; p. 5417
• Main Authors: Zharova, Tatyana V., Grivennikova, Vera G., Borisov, Vitaliy B.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 12.03.2023; MDPI
• Subjects: Antimicrobial agents; ATP synthase; Bacteria; biophysics; Catalysis; Drug resistance; Drugs; E coli; Enzymes; Fo∙F1-ATP synthase/ATPase; Hydrolysis; inhibition; membrane protein; Membrane proteins; molecular bioenergetics; Molecular machines; reversibility of enzyme catalysis; Review
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065417

F1·Fo-ATP synthases/ATPases (F1·Fo) 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 F1·Fo 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 F1·Fo 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” F1·Fo catalysis found in a wide range of bacterial F1·Fo 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.