3jd2

Glutamate dehydrogenase in complex with NADH, open conformation

Loading... Status: waiting for Mol* initialization Structural highlights 3jd2 is a 6 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAI Related: 3jcz, 3jd0, 3jd1, 3jd3, 3jd4 Activity: Glutamate dehydrogenase (NAD(P)(+)), with EC number 1.4.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DHE3_BOVIN] May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). Publication Abstract from PubMed Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping the binding of small-molecule ligands to protein complexes that display conformational flexibility. We illustrate this here using glutamate dehydrogenase (GDH), a 336-kDa metabolic enzyme that catalyzes the oxidative deamination of glutamate. Dysregulation of GDH leads to a variety of metabolic and neurologic disorders. Here, we report near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 A to 3.6 A for GDH complexes, including complexes for which crystal structures are not available. We show that the binding of the coenzyme NADH alone or in concert with GTP results in a binary mixture in which the enzyme is in either an "open" or "closed" state. Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. Our studies thus demonstrate that even in instances when there is considerable structural information available from X-ray crystallography, cryo-EM methods can provide useful complementary insights into regulatory mechanisms for dynamic protein complexes. Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase.,Borgnia MJ, Banerjee S, Merk A, Matthies D, Bartesaghi A, Rao P, Pierson J, Earl LA, Falconieri V, Subramaniam S, Milne JL Mol Pharmacol. 2016 Jun;89(6):645-51. doi: 10.1124/mol.116.103382. Epub 2016 Apr , 1. PMID:27036132 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutamate dehydrogenase 3D structures

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