|
ИСТИНА |
Войти в систему Регистрация |
ИПМех РАН |
||
Inhibitory effects of 7-methylguanine and Its metabolite 8-hydroxy-7-methylguanine on human poly(ADP-ribose) polymerase 1статья
- Авторы: Kurgina T.A., Shram S.I., Kutuzov M.M., Abramova T.V., Shcherbakova T.A., Maltseva E.A., Poroikov V.V., Lavrik O.I., Švedas V.K., Nilov D.K.
- Журнал: Biochemistry (Moscow)
- Том: 87
- Номер: 8
- Год издания: 2022
- Издательство: Pleiades Publishing, Ltd
- Местоположение издательства: Road Town, United Kingdom
- Первая страница: 823
- Последняя страница: 831
- Оригинальные версии: Ингибиторное действие 7-метилгуанина и его метаболита 8-гидрокси-7-метилгуанина на поли(ADP-рибозо)полимеразу 1 человека
- DOI: 10.1134/S0006297922080132
- Аннотация: Previously, we have found that a nucleic acid metabolite, 7-methylguanine (7mGua), produced in the body can have an inhibitory effect on the poly(ADP-ribose) polymerase 1 (PARP1) enzyme, an important pharmacological target in anticancer therapy. In this work, using an original method of analysis of PARP1 activity based on monitoring fluorescence anisotropy, we studied inhibitory properties of 7mGua and its metabolite, 8-hydroxy-7-methylguanine (8h7mGua). Both compounds inhibited PARP1 enzymatic activity in a dose-dependent manner, however, 8h7mGua was shown to be a stronger inhibitor. The IC50 values for 8h7mGua at different concentrations of the NAD+ substrate were found to be 4 times lower, on average, than those for 7mGua. The more efficient binding of 8h7mGua in the PARP1 active site is explained bythe presence of an additional hydrogen bond with the Glu988 catalytic residue. Experimental and computational studies did not reveal the effect of 7mGua and 8h7mGua on the activity of other DNA repair enzymes, indicating selectivity of theirinhibitory action.
- Добавил в систему: Нилов Дмитрий Константинович
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Полный текст | kurgina_eng.pdf | 1,2 МБ | 23 сентября 2023 [nilovdm] |