3JD4: Glutamate Dehydrogenase In Complex With Nadh And Gtp, Closed Conformation

Citation:
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 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.
PDB ID: 3JD4Download
MMDB ID: 138464
PDB Deposition Date: 2016/3/28
Updated in MMDB: 2016/05
Experimental Method:
electron microscopy
Resolution: 3.4  Å
Source Organism:
Similar Structures:
Biological Unit for 3JD4: hexameric; determined by author
Molecular Components in 3JD4
Label Count Molecule
Proteins (6 molecules)
6
Glutamate Dehydrogenase 1, Mitochondrial(Gene symbol: GLUD1)
Molecule annotation
Chemicals (18 molecules)
1
12
2
6
* Click molecule labels to explore molecular sequence information.

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