Reactivation of VX-Inhibited Human Acetylcholinesterase by Deprotonated Pralidoxime. A Complementary Quantum Mechanical Study

Valle da Silva, Jorge Alberto; Pereira, Ander Francisco; Laplante, Steven ORCID: https://orcid.org/0000-0003-2835-5789; Kuca, Kamil; Ramalho, Teodorico Castro et Franca, Tanos Celmar Costa (2020). Reactivation of VX-Inhibited Human Acetylcholinesterase by Deprotonated Pralidoxime. A Complementary Quantum Mechanical Study Biomolecules , vol. 10 , nº 2:192. pp. 1-8. DOI: 10.3390/biom10020192.

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Résumé

In the present work, we performed a complementary quantum mechanical (QM) study to describe the mechanism by which deprotonated pralidoxime (2-PAM) could reactivate human (Homo sapiens sapiens) acetylcholinesterase (HssAChE) inhibited by the nerve agent VX. Such a reaction is proposed to occur in subsequent addition-elimination steps, starting with a nucleophile bimolecular substitution (S(N)2) mechanism through the formation of a trigonal bipyramidal transition state (TS). A near attack conformation (NAC), obtained in a former study using molecular mechanics (MM) calculations, was taken as a starting point for this project, where we described the possible formation of the TS. Together, this combined QM/MM study on AChE reactivation shows the feasibility of the reactivation occurring via attack of the deprotonated form of 2-PAM against the Ser203-VX adduct of HssAChE.

Type de document:	Article
Mots-clés libres:	2-PAM; QM/MM method; VX; acetylcholinesterase
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	18 juill. 2021 23:53
Dernière modification:	11 nov. 2022 15:29
URI:	https://espace.inrs.ca/id/eprint/11571

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