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α-tocopherol, a slow-binding inhibitor of acetylcholinesterase

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dc.contributor.author Zueva I.
dc.contributor.author Lushchekina S.
dc.contributor.author Shulnikova P.
dc.contributor.author Lenina O.
dc.contributor.author Petrov K.
dc.contributor.author Molochkina E.
dc.contributor.author Masson P.
dc.date.accessioned 2022-02-09T20:30:44Z
dc.date.available 2022-02-09T20:30:44Z
dc.date.issued 2021
dc.identifier.issn 0009-2797
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/168656
dc.description.abstract Acetylcholinesterase (AChE) is reversibly inhibited by α-tocopherol (α-T). Steady state kinetic analysis shows that α-T is a mixed slow-binding inhibitor of type A of human enzyme (Kci = 0.49 μM; Kui = 1.6 μM) with a residence time of 2 min on target. Molecular dynamics (MD) simulations support this mechanism, and indicate that α-T first forms multiple non-specific interactions with AChE surface near the gorge entrance, then binds to the peripheral side with alkylene chain slowly sliding down the gorge, inducing no significant conformational change. α-T slightly modulates the progressive inhibition of AChE by the cyclic organophosphorus, cresyl saligenylphosphate, accelerating the fast pseudo-first order process of phosphorylation. A moderate accelerating effect of α-T on phosphorylation by paraoxon was also observed after pre-incubation of AChE in the presence of α-T. This accelerating effect of α-T on ex vivo paraoxon-induced diaphragm muscle weakness was also observed. The effect of α-T on AChE phosphylation was interpreted in light of molecular modeling results. From all results it is clear that α-T does not protect AChE against phosphylation by organophosphorus.
dc.relation.ispartofseries Chemico-Biological Interactions
dc.subject Acetylcholinesterase
dc.subject Molecular modeling
dc.subject Organophosphorus
dc.subject Slow-binding inhibition
dc.subject α-tocopherol
dc.title α-tocopherol, a slow-binding inhibitor of acetylcholinesterase
dc.type Article
dc.relation.ispartofseries-volume 348
dc.collection Публикации сотрудников КФУ
dc.source.id SCOPUS00092797-2021-348-SID85114824145


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  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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