3JD0
Glutamate dehydrogenase in complex with GTP
Summary for 3JD0
| Entry DOI | 10.2210/pdb3jd0/pdb |
| Related | 3JCZ 3JD1 3JD2 3JD3 3JD4 |
| EMDB information | 6630 6631 6632 6633 6634 6635 |
| Descriptor | Glutamate dehydrogenase 1, mitochondrial, GUANOSINE-5'-TRIPHOSPHATE (2 entities in total) |
| Functional Keywords | glutamate metabolism, mitochondria, oxidoreductase |
| Biological source | Bos taurus (bovine) |
| Total number of polymer chains | 6 |
| Total formula weight | 337952.63 |
| Authors | Borgnia, M.J.,Banerjee, S.,Merk, A.,Matthies, D.,Bartesaghi, A.,Rao, P.,Pierson, J.,Earl, L.A.,Falconieri, V.,Subramaniam, S.,Milne, J.L.S. (deposition date: 2016-03-28, release date: 2016-04-27, Last modification date: 2024-02-21) |
| Primary citation | Borgnia, M.J.,Banerjee, S.,Merk, A.,Matthies, D.,Bartesaghi, A.,Rao, P.,Pierson, J.,Earl, L.A.,Falconieri, V.,Subramaniam, S.,Milne, J.L. Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase. Mol.Pharmacol., 89:645-651, 2016 Cited by PubMed Abstract: 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 Å to 3.6 Å 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. PubMed: 27036132DOI: 10.1124/mol.116.103382 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.47 Å) |
Structure validation
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