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Small Angle X-Ray Scattering Studies of Mitochondrial Glutaminase C Reveal Extended Flexible Regions, and Link Oligomeric State with Enzyme Activityстатья
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: 3 декабря 2017 г.
- Авторы: Moller Magda, Nielsen Soren S., Ramachandran Sekar, Yuxing Li, Tria Giancarlo, Streicher Werner, Petoukhov Maxim V., Cerione Richard A., Gillilan Richard E., Vestergaard Bente
- Журнал: PLoS ONE
- Том: 8
- Номер: 9
- Год издания: 2013
- Издательство: Public Library of Science
- Местоположение издательства: United States
- Первая страница: e74783
- DOI: 10.1371/journal.pone.0074783
- Аннотация: Glutaminase C is a key metabolic enzyme, which is unregulated in many cancer systems and believed to play a central role in the Warburg effect, whereby cancer cells undergo changes to an altered metabolic profile. A long-standing hypothesis links enzymatic activity to the protein oligomeric state, hence the study of the solution behavior in general and the oligomer state in particular of glutaminase C is important for the understanding of the mechanism of protein activation and inhibition. In this report, this is extensively investigated in correlation to enzyme concentration or phosphate level, using a high-throughput microfluidic-mixing chip for the SAXS data collection, and we confirm that the oligomeric state correlates with activity. The in-depth solution behavior analysis further reveals the structural behavior of flexible regions of the protein in the dimeric, tetrameric and octameric state and investigates the C-terminal influence on the enzyme solution behavior. Our data enable SAXS-based rigid body modeling of the full-length tetramer states, thereby presenting the first ever experimentally derived structural model of mitochondrial glutaminase C including the N- and C-termini of the enzyme.
- Добавил в систему: Петухов Максим Владимирович