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Composite map of the bGDH di-hexamer in liganded form
Structural highlights
FunctionDHE3_BOVIN May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).[1] Publication Abstract from PubMedGlutamate dehydrogenase (GDH) is a highly regulated key enzyme that catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate, positioning it at a critical hub linking amino acid catabolism to energy production while supplying ammonia for urea synthesis and other nitrogen pathways. Early investigations have shown that bovine GDH (bGDH), which shares 98% sequence identity with its human homolog, assembles into polymeric filaments with altered allosteric responses. Filamentation has only relatively recently been appreciated as a widespread mechanism of enzyme regulation, prompting a reevaluation of these early observations in GDH. Here, we use high-resolution cryogenic electron microscopy (cryo-EM) to show that bGDH hexamers assemble via reciprocal "antenna" interactions that oppose the conformational changes associated with GTP inhibition, revealing how filamentation reshapes GDH allostery and with implications for the treatment of human disease. Structural Mechanism of Filamentation Induced Dampening of GTP Inhibition of Glutamate Dehydrogenase.,Shan Z, Darwish NI, Rivero-Gamez A, Strutzenberg TS, Lyumkis D, Horton NC bioRxiv [Preprint]. 2026 Jul 7:2026.07.06.736867. doi: , 10.64898/2026.07.06.736867. PMID:42465363[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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