Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.

ABSTRACT: Acid-related gastric diseases are associated with disorder of digestive tract acidification. The gastric proton pump, H(+),K(+)-ATPase, exports H(+) in exchange for luminal K(+) to generate a highly acidic environment in the stomach, and is a main target for acid suppressants. Here, we report the three-dimensional structure of gastric H(+),K(+)-ATPase with bound SCH28080, a representative K(+)-competitive acid blocker, at 7 Å resolution based on electron crystallography of two-dimensional crystals. The density of the bound SCH28080 is found near transmembrane (TM) helices 4, 5 and 6, in the luminal cavity. The SCH28080-binding site is formed by the rearrangement of TM helices, which is in turn transmitted to the cytoplasmic domains, resulting in a luminal-open conformation. These results r

SUBMITTER: Abe K 

PROVIDER: S-EPMC3105306 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature