5K12

Cryo-EM structure of glutamate dehydrogenase at 1.8 A resolution

Summary for 5K12

• Entry DOI: 10.2210/pdb5k12/pdb
• Related: 5K0Z 5K10 5K11
• EMDB information: 8191 8192 8193 8194
• Descriptor: Glutamate dehydrogenase 1, mitochondrial (2 entities in total)
• Functional Keywords: glutamate dehydrogenase, small metabolic complex, oxidoreductase
• Biological source: Bos taurus (Bovine)
• Total number of polymer chains: 6
• Total formula weight: 369653.46

Authors

Merk, A.,Bartesaghi, A.,Banerjee, S.,Falconieri, V.,Rao, P.,Earl, L.,Milne, J.,Subramaniam, S. (deposition date: 2016-05-17, release date: 2016-06-08, Last modification date: 2024-03-06)

Primary citation

Merk, A.,Bartesaghi, A.,Banerjee, S.,Falconieri, V.,Rao, P.,Davis, M.I.,Pragani, R.,Boxer, M.B.,Earl, L.A.,Milne, J.L.,Subramaniam, S.
Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery.
Cell, 165:1698-1707, 2016

PubMed 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.

PubMed: 27238019
DOI: 10.1016/j.cell.2016.05.040

Experimental method

ELECTRON MICROSCOPY (1.8 Å)