Репозиторий Университета

Год публикации: Все года 2018 2019 2020

Название	Дата публикации	Коллектив авторов	Журнал	DOI	Индекс цитирования	Ссылка на источник
The preferable binding pose of canonical butyrylcholinesterase substrates is unproductive for echothiophate Butyrylcholinesterase Echothiophate Metadynamics Organophosphates QM/MM	01.01.2018	Zlobin A. Zalevsky A. Mokrushina Y. Kartseva O. Golovin A. Smirnov I.	Acta Naturae		1	Ссылка © 2018 Park-media, Ltd. In this paper, we, for the first time, describe the interaction between the butyrylcholinesterase enzyme and echothiophate, a popular model compound and an analogue of the chemical warfare agents VX and VR, at the atomistic level. Competition between the two echothiophate conformations in the active site was found using molecular modeling techniques. The first one is close to the mode of binding of the substrates of choline series (butyrylcholine and butyrylthiocholine) and is inhibitory, since it is unable to react with the enzyme. The second one is characterized by a significantly worse estimated binding affinity and is reactive. Thus, echothiophate combines the features of two types of inhibitors: competitive and suicidal. This observation will help clarify the kinetic reaction scheme in order to accurately assess the kinetic constants, which is especially important when designing new butyrylcholinesterase variants capable of full-cycle hydrolysis of organophosphorus compounds. Читать тезис