A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1093/protein/gzz039
Entities
People
- Artem Dubovetskyi
- Dan S Tawfik
- Dragana Despotović
- Einav Aharon
- Haim Leader
- Yacov Ashani
Organizations
- Defense Threat Reduction Agency
- United States Department of Defense
- Weizmann Institute of Science