Article
Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.
The Journal of biological chemistry - 1 May 2025
Schwartz Ashley V, Chao Grace, Robinson Mikella, Conley Brittany M, Ahmed Adam Mowaffaq Adam, Wells Grace A, Hoang An, Albekioni Elene, Gallo Cecilia, Weeks Joi, Yunker Katelyn, Quichocho Giovanni, George Uduak Z, Niesman Ingrid, House Carrie D, Turcan Şevin, Sohl Christal D
Abstract excerpt
Mutations in isocitrate dehydrogenase 1 (IDH1) impart a neomorphic reaction that produces D-2-hydroxyglutarate (D2HG), which can inhibit DNA demethylases to drive tumorigenesis. Mutations affect residue R132 and display distinct catalytic profiles for D2HG production. We show that catalytic efficiency of D2HG production is greater in IDH1 R132Q than R132H mutants, and expression of IDH1 R132Q in cellular and...
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