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

被引：54
作者：
Abe, Kazuhiro [1 ]
Tani, Kazutoshi [1 ]
Fujiyoshi, Yoshinori [1 ]
机构：
[1] Kyoto Univ, Dept Biophys, Fac Sci, Sakyo Ku, Kyoto 6060852, Japan
来源：
NATURE COMMUNICATIONS | 2011年 / 2卷
关键词：
K+-COMPETITIVE INHIBITOR; P-TYPE ATPASES; BETA-SUBUNIT; BINDING-SITES; CALCIUM-PUMP; EXTRACELLULAR DOMAIN; ELECTRON-MICROSCOPY; MUTATIONAL ANALYSIS; CRYSTAL-STRUCTURE; SCH; 28080;
D O I：
10.1038/ncomms1154
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 angstrom 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.
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页数：7
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