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Modeling of the enzyme-substrate complexes of human poly(ADP-ribose) polymerase 1статья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 апреля 2020 г.
- Авторы: Nilov D.K., Pushkarev S.V., Gushchina I.V., Manasaryan G.A., Kirsanov K.I., Švedas V.K.
- Журнал: Biochemistry (Moscow)
- Том: 85
- Год издания: 2020
- Издательство: Pleiades Publishing, Ltd
- Местоположение издательства: Road Town, United Kingdom
- Первая страница: 99
- Последняя страница: 107
- DOI: 10.1134/S0006297920010095
- Аннотация: Poly(ADP-ribose) polymerase 1 (PARP-1) is a key DNA repair enzyme and an important target in cancer treatment. Conventional methods of studying the reaction mechanism of PARP-1 have limitations because of the complex structure of PARP1 substrates; however, the necessary data can be obtained by molecular modeling. In this work, a moleculardynamics model for the PARP-1 enzyme–substrate complex containing NAD+molecule and the end of the poly(ADP-ribose) chain in the form of ADP molecule was obtained for the first time. Interactions with the active site residues havebeen characterized where Gly863, Lys903, Glu988 play a crucial role, and the SN1-like mechanism for the enzymatic ADP-ribosylation reaction has been proposed. Models of PARP-1 complexes with more sophisticated two-unit fragments of thegrowing polymer chain as well as competitive inhibitors 3-aminobenzamide and 7-methylguanine have been obtained bymolecular docking.
- Добавил в систему: Нилов Дмитрий Константинович