Department of Medicine, University of Chicago Hospitals, Chicago, IL 60637, USA.
Mar Drugs. 2010 Feb 1;8(2):219-34. doi: 10.3390/md8020219.
Tetrodotoxin and saxitoxin are small, compact asymmetrical marine toxins that block voltage-gated Na channels with high affinity and specificity. They enter the channel pore's outer vestibule and bind to multiple residues that control permeation. Radiolabeled toxins were key contributors to channel protein purification and subsequent cloning. They also helped identify critical structural elements called P loops. Spacial organization of their mutation-identified interaction sites in molecular models has generated a molecular image of the TTX binding site in the outer vestibule and the critical permeation and selectivity features of this region. One site in the channel's domain I P loop determines affinity differences in mammalian isoforms.
河豚毒素和蛤蚌毒素是小型紧凑的非对称海洋毒素，它们以高亲和力和特异性阻断电压门控钠通道。它们进入通道孔的外腔室并与控制渗透的多个残基结合。放射性标记毒素是通道蛋白纯化和随后克隆的关键贡献者。它们还有助于确定称为 P 环的关键结构元素。在分子模型中突变鉴定的相互作用位点的空间组织，生成了外腔室中 TTX 结合位点和该区域关键渗透和选择性特征的分子图像。通道 I 区 P 环中的一个位点决定了哺乳动物同工型中亲和力的差异。
