QM/MM and MM MD simulations on decontamination of the V-type nerve agent VX by phosphotriesterase: toward a comprehensive understanding of steroselectivity and activity
Fangfang Fan, Yongchao Zheng, Yuzhuang Fu, Yuwei Zhang, He Zheng, Changjiang Lyu, Linyu Chen, Jun Huang, Zexing Cao
Abstract
-enantiomer. Further computational analysis on the mutation of selected residues also revealed that H257Y, H257D, H254Q-H257F, and L7ep-3a variants allow more water molecules to enter the active site, which improves the catalytic efficiency of PTE, as observed experimentally. The present work provides mechanistic insights into the stereoselective hydrolysis of VX by PTE and the activity manipulation through the active-site accessibility of water molecules, which can be used for the enzyme engineering to defeat chemical warfare agents.
Topics & Concepts
Nerve agentChemistryEnantiomerHydrolysisCombinatorial chemistryActive siteHuman decontaminationStereospecificityMoleculeBiocatalysisEnzymeStereochemistryStereoselectivityCatalysisOrganic chemistryReaction mechanismAcetylcholinesterasePhysicsNuclear physicsPesticide and Herbicide Environmental StudiesPesticide Exposure and ToxicityInsect Resistance and Genetics