Proton-transporting ATPase (H+-ATPase)

Proton-transporting ATPases are a superfamily of integral membrane enzymes that utilize the energy from ATP hydrolysis to transport protons across biological membranes, establishing electrochemical gradients [1]. This family includes P-type ATPases like the gastric H+/K+-ATPase, V-type ATPases in lysosomes, and F-type ATPases in mitochondria [2]. These enzymes are essential for gastric acidification, bone remodeling, and intracellular pH maintenance [3, 5]. The gastric H+/K+-ATPase is a primary therapeutic target for acid-related disorders like GERD and peptic ulcers, commonly treated with Proton Pump Inhibitors (PPIs) such as omeprazole [4]. V-ATPases are also investigated as targets for osteoporosis and cancer due to their role in extracellular acidification [5]. Drugs targeting these enzymes typically inhibit proton translocation by binding to transmembrane or catalytic domains [6]. The activity of these enzymes is intrinsically linked to their orientation within membrane interfaces, where they couple chemical energy to mechanical proton movement [1].

Other names

H+-ATPaseProton pumpV-ATPaseH+/K+-ATPaseVacuolar ATPaseATP synthaseP-type ATPaseH+-transporting ATPase

Inhibition of the enzyme's ability to transport protons across the membrane, often through covalent binding (as with PPIs) or reversible competition at the ion-binding site [3, 4].