EMD-8194

Single-particle
1.8 Å
EMD-8194 Deposition: 17/05/2016
Map released: 08/06/2016
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-8194

Cryo-EM structure of glutamate dehydrogenase at 1.8 A resolution

EMD-8194

Single-particle
1.8 Å
EMD-8194 Deposition: 17/05/2016
Map released: 08/06/2016
Last modified: 06/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Bos taurus
Sample: Glutamate dehydrogenase
Fitted models: 5k12 (Avg. Q-score: 0.598)

Deposition Authors: Merk A, Bartesaghi A
Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery.
PUBMED: 27238019
DOI: doi:10.1016/j.cell.2016.05.040
ISSN: 1097-4172
Abstract:
Recent advances in single-particle cryoelecton microscopy (cryo-EM) are enabling generation of numerous near-atomic resolution structures for well-ordered protein complexes with sizes ≥ ∼200 kDa. Whether cryo-EM methods are equally useful for high-resolution structural analysis of smaller, dynamic protein complexes such as those involved in cellular metabolism remains an important question. Here, we present 3.8 Å resolution cryo-EM structures of the cancer target isocitrate dehydrogenase (93 kDa) and identify the nature of conformational changes induced by binding of the allosteric small-molecule inhibitor ML309. We also report 2.8-Å- and 1.8-Å-resolution structures of lactate dehydrogenase (145 kDa) and glutamate dehydrogenase (334 kDa), respectively. With these results, two perceived barriers in single-particle cryo-EM are overcome: (1) crossing 2 Å resolution and (2) obtaining structures of proteins with sizes < 100 kDa, demonstrating that cryo-EM can be used to investigate a broad spectrum of drug-target interactions and dynamic conformational states.