title: Functional domains of the gastric HK ATPase.
abstract: The gastric H+ + K+ ATPase is a member of the phosphorylating class of transport ATPase. Based on sequence homologies and CHO content, there may be a b subunit associated with the catalytic subunit of the H+ + K+ ATPase. Its function, if present, is unknown. The pump catalyzes a stoichiometric exchange of H+ for K+, but is also able to transport Na+ in the forward direction. This suggests that the transport step involves hydronium rather than protons. The initial binding site is likely to contain a histidine residue to account for the high affinity of the cellular site. The extracellular site probably lacks this histidine, so that a low affinity for hydronium allows release into a solution of pH 0.8. Labelling with positively charge, luminally reactive reagents that block ATPase and pump activity has shown that a region containing H5 and H6 and the intervening luminal loop is involved in necessary conformational changes for normal pump activity. The calculated structure of this loop shows the presence of an a helical, b turn, and b strand sector, with negative charges close to the membrane domain. This sector provides a possible site of interaction of drugs with the H+ + K+ ATPase, and may be part of the K+ pathway in the enzyme.
authors.affiliation: University of California, Los Angeles.
authors.forename: G
authors.initials: G
authors.lastname: Sachs
authors.forename: K
authors.initials: K
authors.lastname: Munson
authors.forename: V N
authors.initials: VN
authors.lastname: Balaji
authors.forename: D
authors.initials: D
authors.lastname: Aures-Fischer
authors.forename: S J
authors.initials: SJ
authors.lastname: Hersey
authors.forename: K
authors.initials: K
authors.lastname: Hall
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D017506:H(+)-K(+)-Exchanging ATPase; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D013270:Stomach / Q000201:enzymology*; D013552:Swine
chemical_list: D046911:Macromolecular Substances; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase