| Форма представления | Статьи в зарубежных журналах и сборниках |
| Год публикации | 2016 |
| Язык | русский |
|
Петров Константин Александрович, автор
|
| Библиографическое описание на языке оригинала |
Kharlamova A.D. Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: Mechanism and possible advantages for myasthenia gravis treatment / A.D. Kharlamova, S.V. Lushchekina, K.A. Petrov, E.D. Kots, F.Nachon, M. Villard-Wandhammer, I.V. Zueva, E. Krejci, V.S. Reznik, V.V. Zobov, E.E. Nikolsky, P. Masson // Biochemical Journal, Volume 473, Issue 9, 1 May 2016, Pages 1225-1236 |
| Аннотация |
Inhibition of human AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) by an alkylammonium derivative of 6-methyluracil, C-547, a potential drug for the treatment of MG (myasthenia gravis) was studied. Kinetic analysis of AChE inhibition showed that C-547 is a slow-binding inhibitor of type B, i.e. after formation of the initial enzyme?inhibitor complex (Ki = 140 pM), an induced-fit step allows establishment of the final complex (Ki = 22 pM). The estimated koff is low, 0.05 -1 . On the other hand, reversible inhibition of human BChE is a fast-binding process of mixed-type (Ki = 1.77 μM; Ki = 3.17 μM). The crystal structure of mouse AChE complexed with C-547 was solved at 3.13 Å resolution. The complex is stabilized by cation-π , stacking and hydrogenbonding interactions. Molecular dynamics simulations of the binding/dissociation processes of C-547 and C-35 (a noncharged analogue) to mouse and human AChEs were performed. |
| Ключевые слова |
6-methyluracil; Acetylcholinesterase; Butyrylcholinesterase; Molecular modelling; Slow-binding inhibition; X-ray structure. |
| Название журнала |
BIOCHEMICAL JOURNAL
|
| Пожалуйста, используйте этот идентификатор, чтобы цитировать или ссылаться на эту карточку |
https://repository.kpfu.ru/?p_id=136583 |
Полная запись метаданных  |
| Поле DC |
Значение |
Язык |
| dc.contributor.author |
Петров Константин Александрович |
ru_RU |
| dc.date.accessioned |
2016-01-01T00:00:00Z |
ru_RU |
| dc.date.available |
2016-01-01T00:00:00Z |
ru_RU |
| dc.date.issued |
2016 |
ru_RU |
| dc.identifier.citation |
Kharlamova A.D. Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: Mechanism and possible advantages for myasthenia gravis treatment / A.D. Kharlamova, S.V. Lushchekina, K.A. Petrov, E.D. Kots, F.Nachon, M. Villard-Wandhammer, I.V. Zueva, E. Krejci, V.S. Reznik, V.V. Zobov, E.E. Nikolsky, P. Masson // Biochemical Journal, Volume 473, Issue 9, 1 May 2016, Pages 1225-1236 |
ru_RU |
| dc.identifier.uri |
https://repository.kpfu.ru/?p_id=136583 |
ru_RU |
| dc.description.abstract |
BIOCHEMICAL JOURNAL |
ru_RU |
| dc.description.abstract |
Inhibition of human AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) by an alkylammonium derivative of 6-methyluracil, C-547, a potential drug for the treatment of MG (myasthenia gravis) was studied. Kinetic analysis of AChE inhibition showed that C-547 is a slow-binding inhibitor of type B, i.e. after formation of the initial enzyme?inhibitor complex (Ki = 140 pM), an induced-fit step allows establishment of the final complex (Ki = 22 pM). The estimated koff is low, 0.05 -1 . On the other hand, reversible inhibition of human BChE is a fast-binding process of mixed-type (Ki = 1.77 μM; Ki = 3.17 μM). The crystal structure of mouse AChE complexed with C-547 was solved at 3.13 Å resolution. The complex is stabilized by cation-π , stacking and hydrogenbonding interactions. Molecular dynamics simulations of the binding/dissociation processes of C-547 and C-35 (a noncharged analogue) to mouse and human AChEs were performed. |
ru_RU |
| dc.language.iso |
ru |
ru_RU |
| dc.subject |
|
ru_RU |
| dc.title |
Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: Mechanism and possible advantages for myasthenia gravis treatment |
ru_RU |
| dc.type |
Статьи в зарубежных журналах и сборниках |
ru_RU |
|
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