Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.
Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.
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DOI：
10.1038/ncomms1154
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发表时间：
2011-01-11
影响因子：
16.6
通讯作者：
Fujiyoshi Y
中科院分区：
文献类型：
--
作者：
Abe K;Tani K;Fujiyoshi Y
酸相关性胃病与消化道酸化障碍有关。胃质子泵，H+，K+-ATP酶，输出H+以交换管腔K+，从而在胃中产生高度酸性的环境，并且是酸抑制剂的主要靶标。在这里，我们报告的三维结构的胃H+，K+-ATP酶结合SCH 28080，一个代表性的K+-竞争性酸阻断剂，在7 μ m分辨率的基础上的二维晶体的电子晶体学。结合的SCH 28080的密度在管腔中的跨膜（TM）螺旋4、5和6附近发现。SCH 28080结合位点是由TM螺旋重排形成的，TM螺旋又被传递到细胞质结构域，导致管腔开放构象。这些结果代表了酸抑制剂在H+，K+-ATP酶上的结合位点的第一个结构证据，以及这类药物引起的构象变化。胃质子泵，H+，K+-ATP酶，有助于胃酸化，是酸抑制剂的靶点。在这里，使用电子晶体学确定泵的三维结构，提供了关于一类新的酸抑制剂的结合的第一个结构信息。
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 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. The gastric proton pump, H+,K+-ATPase, contributes to stomach acidification and is a target of acid suppressants. Here, the three-dimensional structure of the pump is determined using electron crystallography, providing the first structural information about the binding of a new class of acid suppressants.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Asano, S;Matsuda, S;Takeguchi, N
通讯作者：
Takeguchi, N
影响因子：
2.9
作者：
Munson, K;Garcia, R;Sachs, G
通讯作者：
Sachs, G
影响因子：
3
作者：
Crowther, RA;Henderson, R;Smith, JM
通讯作者：
Smith, JM
影响因子：
11.4
作者：
Abe, Kazuhiro;Tani, Kazutoshi;Fujiyoshi, Yoshinori
通讯作者：
Fujiyoshi, Yoshinori