Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase.
Journal, issue, pages	Mol Pharmacol, Vol. 89, Issue 6, Page 645-651, Year 2016
Publish date	Apr 1, 2016
Authors	Mario J Borgnia / Soojay Banerjee / Alan Merk / Doreen Matthies / Alberto Bartesaghi / Prashant Rao / Jason Pierson / Lesley A Earl / Veronica Falconieri / Sriram Subramaniam / Jacqueline L S Milne /
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 ...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.
External links	Mol Pharmacol / PubMed:27036132 / PubMed Central
Methods	EM (single particle)
Resolution	3.26 - 3.6 Å
Structure data	6630 3jcz EMDB-6630: Glutamate dehydrogenase in the unliganded state PDB-3jcz: Structure of bovine glutamate dehydrogenase in the unliganded state Method: EM (single particle) / Resolution: 3.26 Å 6631 3jd0 EMDB-6631, PDB-3jd0: Glutamate dehydrogenase in complex with GTP Method: EM (single particle) / Resolution: 3.47 Å 6632 3jd3 EMDB-6632, PDB-3jd3: Glutamate dehydrogenase in complex with NADH and GTP, open conformation Method: EM (single particle) / Resolution: 3.6 Å 6633 3jd4 EMDB-6633, PDB-3jd4: Glutamate dehydrogenase in complex with NADH and GTP, closed conformation Method: EM (single particle) / Resolution: 3.4 Å 6634 3jd1 EMDB-6634, PDB-3jd1: Glutamate dehydrogenase in complex with NADH, closed conformation Method: EM (single particle) / Resolution: 3.3 Å 6635 3jd2 EMDB-6635, PDB-3jd2: Glutamate dehydrogenase in complex with NADH, open conformation Method: EM (single particle) / Resolution: 3.3 Å
Chemicals	ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM ChemComp-NAI*: 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE
Source	bos taurus (cattle) unidentified (others)
Keywords	OXIDOREDUCTASE / glutamate metabolism / mitochondria