9ZQT

Composite map of the bGDH di-hexamer in liganded form

Summary for 9ZQT

• Entry DOI: 10.2210/pdb9zqt/pdb
• EMDB information: 74581
• Descriptor: Glutamate dehydrogenase 1, mitochondrial, GUANOSINE-5'-TRIPHOSPHATE, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: glutamate dehydrogenase amino acid metabolism filament allosteric regulation, unknown function
• Biological source: Bos taurus (domestic cattle)
• Total number of polymer chains: 12
• Total formula weight: 762257.50

Authors

Shan, Z.,Lyumkis, D. (deposition date: 2025-12-19, release date: 2026-07-29)

Primary citation

Shan, Z.,Darwish, N.I.,Rivero-Gamez, A.,Strutzenberg, T.S.,Lyumkis, D.,Horton, N.C.
Structural Mechanism of Filamentation Induced Dampening of GTP Inhibition of Glutamate Dehydrogenase.
Biorxiv, 2026

PubMed Abstract: Glutamate dehydrogenase (GDH) is a highly regulated key enzyme that catalyzes the reversible oxidative deamination of glutamate to α-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.

PubMed: 42465363
DOI: 10.64898/2026.07.06.736867

Experimental method

ELECTRON MICROSCOPY (3.5 Å)