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A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents.
Protein Engineering, Design and Selection ( IF 2.6 ) Pub Date : 2019-10-15 , DOI: 10.1093/protein/gzz039
Dragana Despotović 1 , Einav Aharon 1 , Artem Dubovetskyi 1 , Haim Leader 1 , Yacov Ashani 1 , Dan S Tawfik 1
Affiliation  

Nerve agents are organophosphates (OPs) that potently inhibit acetylcholinesterase, and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase (Bd-PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents-GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd-PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme 'cocktail' comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.

中文翻译:

三种工程磷酸三酯酶的混合物可对已知威胁神经毒剂的整个光谱进行快速排毒。

神经药物是有效抑制乙酰胆碱酯酶的有机磷酸酯(OPs),它们的酶解毒作用一直是一个长期的目标。神经剂的大小,电荷,疏水性和可裂解的酯键变化很大。因此,单一酶不太可能有效地水解所有试剂。在这里,我们描述了三种以前开发的细菌磷酸三酯酶(Bd-PTE)变体的混合物,这些变体高度稳定且几乎具有相同的序列。这种混合物可以有效地排毒多种已知的威胁因子,例如GA(tabun),GB(sarin),GD(soman),GF(cyclosarin),VX和Russian-VX。可能使Bd-PTE失活的二聚体解离和交换的可能性影响很小,并且三种酶变体在混合物中的活性与它们各自的活性相同。据我们所知,
更新日期:2020-04-17
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