Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, 91220 Brétigny-sur-Orge, France.
Molecules. 2021 Jan 27;26(3):657. doi: 10.3390/molecules26030657.
Organophosphorous nerve agents (OPNA) pose an actual and major threat for both military and civilians alike, as an upsurge in their use has been observed in the recent years. Currently available treatments mitigate the effect of the nerve agents, and could be vastly improved by means of scavengers of the nerve agents. Consequently, efforts have been made over the years into investigating enzymes, also known as bioscavengers, which have the potential either to trap or hydrolyze these toxic compounds. We investigated the previously described esterase 2 from (TtEst2) as a potential bioscavenger of nerve agents. As such, we assessed its potential against G-agents (tabun, sarin, and cyclosarin), VX, as well as the pesticide paraoxon. We report that TtEst2 is a good bioscavenger of paraoxon and G-agents, but is rather slow at scavenging VX. X-ray crystallography studies showed that TtEst2 forms an irreversible complex with the aforementioned agents, and allowed the identification of amino-acids, whose mutagenesis could lead to better scavenging properties for VX. In conjunction with its cheap production and purification processes, as well as a robust structural backbone, further engineering of TtEst2 could lead to a stopgap bioscavenger useful for in corpo scavenging or skin decontamination.
有机磷神经毒剂（OPNA）对军事和民用都构成了实际且重大的威胁，因为近年来观察到其使用有所增加。目前可用的治疗方法可以减轻神经毒剂的影响，通过神经毒剂清除剂可以得到极大的改善。因此，多年来人们一直在研究酶，也称为生物清除剂，这些酶具有捕获或水解这些有毒化合物的潜力。我们研究了先前描述的来自 （TtEst2）的酯酶 2 作为神经毒剂的潜在生物清除剂。因此，我们评估了它对 G 剂（塔崩、沙林和梭曼）、VX 以及杀虫剂对氧磷的潜在作用。我们报告说，TtEst2 是对氧磷和 G 剂的良好生物清除剂，但对 VX 的清除速度相当慢。X 射线晶体学研究表明，TtEst2 与上述试剂形成不可逆复合物，并确定了氨基酸，其诱变可能导致对 VX 具有更好的清除性能。结合其廉价的生产和纯化工艺以及坚固的结构骨架，进一步对 TtEst2 进行工程改造可能会产生一种用于体内清除或皮肤去污的临时生物清除剂。
