Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.

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, h...

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Autores principales:	Magda Møller, Søren S Nielsen, Sekar Ramachandran, Yunxing Li, Giancarlo Tria, Werner Streicher, Maxim V Petoukhov, Richard A Cerione, Richard E Gillilan, Bente Vestergaard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9682e391a4e9416baea413fc6257853a
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spelling	oai:doaj.org-article:9682e391a4e9416baea413fc6257853a2021-11-18T08:53:08ZSmall angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.1932-620310.1371/journal.pone.0074783https://doaj.org/article/9682e391a4e9416baea413fc6257853a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098668/?tool=EBIhttps://doaj.org/toc/1932-6203Glutaminase 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.Magda MøllerSøren S NielsenSekar RamachandranYunxing LiGiancarlo TriaWerner StreicherMaxim V PetoukhovRichard A CerioneRichard E GillilanBente VestergaardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74783 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Magda Møller Søren S Nielsen Sekar Ramachandran Yunxing Li Giancarlo Tria Werner Streicher Maxim V Petoukhov Richard A Cerione Richard E Gillilan Bente Vestergaard Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.
description	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.
format	article
author	Magda Møller Søren S Nielsen Sekar Ramachandran Yunxing Li Giancarlo Tria Werner Streicher Maxim V Petoukhov Richard A Cerione Richard E Gillilan Bente Vestergaard
author_facet	Magda Møller Søren S Nielsen Sekar Ramachandran Yunxing Li Giancarlo Tria Werner Streicher Maxim V Petoukhov Richard A Cerione Richard E Gillilan Bente Vestergaard
author_sort	Magda Møller
title	Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.
title_short	Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.
title_full	Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.
title_fullStr	Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.
title_full_unstemmed	Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.
title_sort	small angle x-ray scattering studies of mitochondrial glutaminase c reveal extended flexible regions, and link oligomeric state with enzyme activity.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9682e391a4e9416baea413fc6257853a
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Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.

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