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Glycation of alpha-synuclein amplifies the binding with glyceraldehyde-3-phosphate dehydrogenaseстатья
Статья опубликована в высокорейтинговом журнале
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: 10 апреля 2019 г.
- Авторы: Semenyuk Pavel, Barinova Kseniya, Muronetz Vladimir
- Журнал: International Journal of Biological Macromolecules
- Том: 127
- Год издания: 2019
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 278
- Последняя страница: 285
- DOI: 10.1016/j.ijbiomac.2019.01.064
- Аннотация: α-Synuclein was recently found to interact with moonlighting glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) involved in neurodegenerative diseases development. In the present work, we have analyzed influence of α-synuclein glycation on this interaction, because the literature data suggest relation between diabetes and Parkinson's disease. According to zeta potential measurement, glycation can shift the charge of α-synuclein to more negative values that was pronounced in case of modification by glyceraldehyde-3-phosphate. We selected carboxymethyl lysine as a typical advanced glycation end product and performed molecular dynamics simulations. The binding was found to be electrostatically driven and was significantly amplified after α-synuclein glycation because of increase the number of acidic residues. Since the main binding site was located in the anion-binding groove, which comprises the active site of GAPDH, enhanced binding of α-synuclein can result in GAPDH inactivation. This hypothesis was proven experimentally. Glycation of α-synuclein resulted in increase of GAPDH inactivation, and this effect was more pronounced in case of modification by glyceraldehyde-3-phosphate. The obtained results can reflect the probable relations between protein glycation and neurodegenerative diseases.
- Добавил в систему: Семенюк Павел Игоревич