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 |
|