Bacterial F-type ATP synthase (F-ATPase)

Bacterial F-type ATP synthase, also known as F1F0-ATPase, is a complex, multi-subunit enzyme essential for the survival of bacteria by serving as the primary source of cellular energy (1.1.1, 1.3.2). It operates as a rotary motor that couples the movement of protons across the bacterial plasma membrane to the synthesis of adenosine triphosphate (ATP) from ADP and inorganic phosphate (1.3.1, 1.5.2). In many pathogenic species, such as Mycobacterium tuberculosis, the enzyme is critical for maintaining energy homeostasis in both actively growing and dormant states (1.2.2, 1.5.1). Therapeutic agents like bedaquiline target this enzyme with high specificity, binding to the c-ring or the epsilon subunit to stall the rotation required for ATP production (1.2.1, 1.2.4). This inhibition results in rapid ATP depletion and bacterial death, making it a validated target for treating multidrug-resistant tuberculosis (1.1.2, 1.5.5). A significant challenge in drug development is ensuring high selectivity for the bacterial enzyme over the structurally similar human mitochondrial F-ATPase to minimize host toxicity (1.1.5, 1.3.2).

Other names

F1F0-ATPaseF-type ATPaseATP synthaseH+-transporting two-sector ATPaseProton-translocating ATP synthaseBacterial ATP synthase

Inhibition of the rotary mechanism of the F-type ATP synthase by binding to the c-ring (stalling rotation) or the epsilon subunit (disrupting coupling), which prevents ATP synthesis and leads to the depletion of cellular energy stores.