Structural highlights
Disease
[ATP4B_PIG] Note=Parietal cell autoantigen associated with autoimmune gastritis.
Function
[ATP4A_PIG] Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach.
Publication Abstract from PubMed
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 A 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 represent the first structural evidence for a binding site of an acid suppressant on H(+),K(+)-ATPase, and the conformational change induced by this class of drugs.
Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.,Abe K, Tani K, Fujiyoshi Y Nat Commun. 2011 Jan;2(1):155. PMID:21224846[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Abe K, Tani K, Fujiyoshi Y. Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant. Nat Commun. 2011 Jan;2(1):155. PMID:21224846 doi:10.1038/ncomms1154
