sodium/potassium-ATPase α3 Inhibitors

Chemical inhibitors of sodium/potassium-ATPase α3 function by binding to specific sites on the protein and altering its activity. Ouabain acts by specifically binding to the protein, which blocks its ability to exchange sodium and potassium ions across the cell membrane, a critical function for maintaining the electrochemical gradient essential to cellular processes. Digoxin and digitoxin share a similar mechanism, inhibiting the protein by binding to its extracellular domain and the same site as endogenous cations, respectively, preventing the enzyme from carrying out its ion transport function. This disruption in ionic homeostasis affects cellular electrical activity. Digoxigenin, on the other hand, competes for the cardiac glycoside binding site on the sodium/potassium-ATPase α3, disrupting the necessary conformational changes for the pump's function.

Continuing with other inhibitors, oleandrin, bufalin, and marinobufagenin selectively inhibit sodium/potassium-ATPase α3 by binding to the enzyme and stabilizing specific conformations or preventing crucial steps in the enzyme cycle. Oleandrin prevents the enzyme from conducting necessary ion exchanges, bufalin stabilizes the E2 conformation, and marinobufagenin prevents the conformational change required for ATP hydrolysis and ion transport. Peruvoside inhibits the phosphorylation step necessary for ion transport, impairing the pump's ability to maintain electrochemical gradients. Similarly, telocinobufagin, proscillaridin A, and cymarin affect the sodium/potassium-ATPase α3 by binding to the active site or specific ion sites, hindering the enzyme's ability to cycle through its conformational states or blocking the ion transport cycle, thus halting the pump's function and maintaining intracellular ion concentrations. Convallatoxin also inhibits sodium/potassium-ATPase α3 by binding to the K+ binding site, preventing necessary conformational changes for ion transport. Through these various methods of action, each chemical inhibitor disrupts the ion transport mechanism critical to the proper functioning of the sodium/potassium-ATPase α3.