Van Theemsche Kenny M, Van de Sande Dieter V, Snyders Dirk J, Labro Alain J
Laboratory of Molecular, Cellular, and Network Excitability, University of Antwerp, Antwerp, Belgium.
Front Pharmacol. 2020 May 15;11:735. doi: 10.3389/fphar.2020.00735. eCollection 2020.
In the Na channel family the lipophilic drugs/toxins binding sites and the presence of fenestrations in the channel pore wall are well defined and categorized. No such classification exists in the much larger K channel family, although certain lipophilic compounds seem to deviate from binding to well-known hydrophilic binding sites. By mapping different compound binding sites onto 3D structures of Kv channels, there appear to be three distinct lipid-exposed binding sites preserved in K channels: the front and back side of the pore domain, and S2-S3/S3-S4 clefts. One or a combination of these sites is most likely the orthologous equivalent of neurotoxin site 5 in Na channels. This review describes the different lipophilic binding sites and location of pore wall fenestrations within the K channel family and compares it to the knowledge of Na channels.
在钠通道家族中，亲脂性药物/毒素结合位点以及通道孔壁上窗孔的存在已得到明确界定和分类。在规模大得多的钾通道家族中则不存在这样的分类，尽管某些亲脂性化合物似乎偏离了与众所周知的亲水性结合位点的结合。通过将不同化合物结合位点映射到钾通道的三维结构上，钾通道中似乎保留了三个不同的脂质暴露结合位点：孔结构域的正面和背面，以及S2-S3/S3-S4裂隙。这些位点中的一个或组合很可能是钠通道中神经毒素位点5的直系同源等效物。本综述描述了钾通道家族中不同的亲脂性结合位点和孔壁窗孔的位置，并将其与钠通道的知识进行比较。
