Structural and Functional Integrity of H,K-ATPase Depends β-Subunit
The primary gastric H+ pump, the H,K-ATPase, belongs to the family of cation pump enzymes called P-type ATPases, which include the Na,K-ATPase and the Ca-ATPase (Jørgenson & Andersen 1988; Inesi & Kirtley 1992). This family of pump proteins all have the ability to form a phosphoenzyme intermediate, or E-P, in their catalytic cylcle, and predictably, they share a relatively high degree of sequence homology. Among the P-type ATPases, the H,K-ATPase and the Na,K-ATPase have the highest degree of homology (~60% identity), sharing at least two additional unique features: they are both cation exchange transporters, involving the cellular uptake of K+ in exchange for the respective Na+ or H+ export from the cell; and both pumps consist of αβ-subunit heterodimers. The α-subunits of both Na,K- and H, K-ATPase have eight transmembrane segments, and ~70% of the 110 kDa mass is distributed within the cytoplasmic domain where ATP binding and phosphoenzyme formation occur. Thus the α-subunit is frequently called the catalytic subunit of the respective enzyme. The α-subunit of the Na,K- ATPase contains the ouabain binding site localized to the extracellular domain (Lingrel 1992). Although the H,K-ATPase does not bind ouabain, an omeprazole binding site has been localized to the extracellular domain of its a-subunit (Sachs et al. 1989).
KeywordsHydrolysis Titration Cysteine Disulfide Butanol
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