P-type ATPase

P-type ATPases are a large superfamily of integral membrane proteins that utilize the energy from ATP hydrolysis to transport cations and lipids across biological membranes against their concentration gradients. They are defined by a unique catalytic mechanism that involves the formation of a transient phosphorylated aspartate intermediate and a cycle of conformational changes between E1 and E2 states. This family includes essential human transporters such as the sodium-potassium pump (Na+/K+-ATPase), the gastric proton pump (H+/K+-ATPase), and various calcium pumps (SERCA and PMCA). These proteins play fundamental roles in maintaining cellular homeostasis, including the regulation of membrane potential, intracellular pH, and calcium signaling. Malfunction or mutation of P-type ATPases is associated with diverse pathologies, such as heart failure, gastric ulcers, Wilson's disease, and various neurological disorders. As a result, they are prominent therapeutic targets; for instance, proton pump inhibitors (PPIs) are used to treat acid-related gastrointestinal diseases, while cardiac glycosides like digoxin are employed in managing cardiovascular conditions. Ongoing research also explores their potential as targets for novel antimicrobial and anticancer therapies.

Other names

E1-E2 ATPaseP-type adenosine triphosphataseP-ATPasePhosphorylation-type ATPase

Inhibition of active ion transport by binding to specific conformational states (E1 or E2) of the ATPase, thereby preventing the ATP-driven translocation of cations across the membrane.