Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501, Costa Rica.
Toxicon. 2012 Sep 15;60(4):520-30. doi: 10.1016/j.toxicon.2012.02.007. Epub 2012 Mar 3.
Snake venoms often contain toxins that cause a rapid necrosis of skeletal muscle fibers, referred to as myotoxins. The most common among them are phospholipases A(2) (PLA(2)s), enzymes that have two independent evolutionary origins in snake venoms. Within the group II PLA(2)s found in viperid venoms, a particular subgroup emerged, in which the otherwise conserved Asp49 of their catalytic center is replaced by Lys49. These intriguing proteins, referred to as Lys49 myotoxins, lost the ability to catalyze phospholipid hydrolysis, but still induce myonecrosis by a non-enzymatic mechanism based on membrane permeabilization as the critical event. Such mechanism is only partially understood. This review briefly describes the general structural and functional characteristics of the Lys49 myotoxins, and summarizes four proposed models of their functional "toxic site". Finally, it discusses some novel insights into their mode of action, in particular examining arguments and experimental observations that could shed light on the possible nature of their membrane target on skeletal muscle cells, which remains elusive.
蛇毒通常含有导致骨骼肌纤维迅速坏死的毒素，称为肌毒素。其中最常见的是磷脂酶 A2（PLA2s），它们在蛇毒中有两个独立的进化起源。在蝰蛇毒液中发现的 II 组 PLA2s 中，出现了一个特殊的亚组，其中催化中心原本保守的天冬氨酸 49 被赖氨酸 49 取代。这些引人关注的蛋白质被称为赖氨酸 49 肌毒素，它们失去了催化磷脂水解的能力，但仍然通过基于膜通透性的非酶机制诱导肌坏死，这是关键事件。这种机制还不完全清楚。本文简要描述了赖氨酸 49 肌毒素的一般结构和功能特征，并总结了它们功能“毒性位点”的四个假设模型。最后，它讨论了对其作用模式的一些新见解，特别是检查了一些论点和实验观察，这些论点和实验观察可能有助于阐明它们在骨骼肌细胞上的膜靶标的可能性质，而这仍然难以捉摸。
