Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site.
Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site.
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DOI：
10.1021/bi500525s
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发表时间：
2014-08-19
期刊：
影响因子：
2.9
通讯作者：
Gross A
中科院分区：
文献类型：
--
作者：
Lenaeus MJ;Burdette D;Wagner T;Focia PJ;Gross A
钾通道允许钾离子在细胞膜上被动移动，并有助于控制所有类型细胞的膜电位。季铵(QA)化合物阻断钾通道，长期以来一直被用来研究这些通道的功能和结构特性。在这里，我们描述了三个对称疏水的QA与原核生物钾通道KCsA的相互作用。这些结构证明了KCSA内螺旋之间存在疏水口袋，并提供了对疏水QAS的结合位置和封闭机制的深入了解。这些结构还揭示了中央空腔和外部膜环境之间的结构隐藏路径，这让人想起在钠通道中观察到的侧窗，可以通过孔壁的小构象变化进入。我们认为，疏水结合口袋稳定了长链QA分子的烷基链，并可能在疏水药物结合中发挥关键作用。
Potassium channels allow for the passive movement of potassium ions across the cell membrane and are instrumental in controlling the membrane potential in all cell types. Quaternary ammonium (QA) compounds block potassium channels and have long been used to study the functional and structural properties of these channels. Here we describe the interaction between three symmetrical hydrophobic QAs and the prokaryotic potassium channel KcsA. The structures demonstrate the presence of a hydrophobic pocket between the inner helices of KcsA and provide insight into the binding site and blocking mechanism of hydrophobic QAs. The structures also reveal a structurally hidden pathway between the central cavity and the outside membrane environment reminiscent of the lateral fenestration observed in sodium channels that can be accessed through small conformational changes in the pore wall. We propose that the hydrophobic binding pocket stabilizes the alkyl chains of long-chain QA molecules and may play a key role in hydrophobic drug binding in general.
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影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1085/jgp.59.4.388
发表时间：
1972-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Armstrong CM;Hille B
通讯作者：
Hille B
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
3.8
作者：
Holmgren, M;Smith, PL;Yellen, G
通讯作者：
Yellen, G
DOI：
10.1085/jgp.58.4.413
发表时间：
1971-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Armstrong CM
通讯作者：
Armstrong CM