FIGURE 5.

Conformational changes of the H⁺-K⁺-ATPase. Phosphorylation and dephosphorylation of the gastric H⁺-K⁺-ATPase results in conformational changes facilitating the transport of H₃O⁺ out of parietal cells concurrently with influx of K⁺. Initially, a hydronium ion binds the cytoplasmic surface of the H⁺-K⁺-ATPase and MgATP phosphorylates the protein to form the E₁ conformation. In the E₁ form, the ion-binding site faces the parietal cell cytoplasm. Next, the E₁ form undergoes a conformational change to the E₂ form where the ion binding site faces the gastric lumen. In this position the H₃O⁺ is released into the gastric lumen. In this E₂ conformation, K⁺ binds the ion site where H₃O⁺ was previously bound. The enzyme is dephosphorylated, and a conformational change back to the E₁ form results in the ion binding site facing the parietal cell cytoplasm where K⁺ is displaced by ATP binding (386, 387). Based on work on the Na⁺-K⁺-ATPase under physiological conditions, the E₂ to E₁ conformational transition of the unphosphorylated enzyme is postulated to be the rate-limiting step (232).