Kuldyushev Nikita A, Berkut Antonina A, Peigneur Steve, Tytgat Jan, Grishin Eugene V, Vassilevski Alexander A
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow Institute of Physics and Technology (State University), Russia.
FEBS Lett. 2017 Oct;591(20):3414-3420. doi: 10.1002/1873-3468.12839. Epub 2017 Sep 21.
Scorpion α-toxins are polypeptides that inhibit voltage-gated sodium channel inactivation. They are divided into mammal, insect and α-like toxins based on their relative activity toward different phyla. Several factors are currently known to influence the selectivity, which are not just particular amino acid residues but also general physical, chemical, and topological properties of toxin structural modules. The objective of this study was to change the selectivity profile of a chosen broadly active α-like toxin, BeM9 from Mesobuthus eupeus, toward mammal-selective. Based on the available information on what determines scorpion α-toxin selectivity, we designed and produced msBeM9, a BeM9 derivative, which was verified to be exclusively active toward mammalian sodium channels and, most importantly, toward the Na 1.2 isoform expressed in the brain.
蝎α-毒素是抑制电压门控钠通道失活的多肽。根据它们对不同门类的相对活性，可分为哺乳动物毒素、昆虫毒素和α样毒素。目前已知有几个因素会影响选择性，这些因素不仅包括特定的氨基酸残基，还包括毒素结构模块的一般物理、化学和拓扑性质。本研究的目的是改变一种选定的具有广泛活性的α样毒素——东亚钳蝎的BeM9对哺乳动物的选择性。基于有关决定蝎α-毒素选择性的现有信息，我们设计并制备了msBeM9，一种BeM9衍生物，经证实它仅对哺乳动物钠通道有活性，最重要的是，对大脑中表达的Na 1.2亚型有活性。
