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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 |