Thuy-Tien Thi Nguyen
Postdoctoral Scholar, Biochemistry
Honors & Awards
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MCHRI Postdoctoral Award, Stanford Maternal & Child Health Research Institute (2024)
Professional Education
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Doctor of Philosophy, Cornell University (2022)
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Master of Science, Cornell University (2020)
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Bachelor of Science, Korea Advanced Institute of Science & Technology (KAIST) (2017)
All Publications
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Filament formation drives catalysis by glutaminase enzymes important in cancer progression
NATURE COMMUNICATIONS
2024; 15 (1): 1971
Abstract
The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the 'glutamine addiction' of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide a view of the conformational states essential for catalysis. Filament formation guides an 'activation loop' to assume a specific conformation that works together with a 'lid' to close over the active site and position glutamine for nucleophilic attack by an essential serine. Our findings highlight how ankyrin repeats on GLS2 regulate enzymatic activity, while allosteric activators stabilize, and clinically relevant inhibitors block, filament formation that enables glutaminases to catalyze glutaminolysis and support cancer progression.
View details for DOI 10.1038/s41467-024-46351-3
View details for Web of Science ID 001179853600006
View details for PubMedID 38438397
View details for PubMedCentralID PMC10912226