3JD1

Glutamate dehydrogenase in complex with NADH, closed conformation

3JD1 の概要

• エントリーDOI: 10.2210/pdb3jd1/pdb
• 関連するPDBエントリー: 3JCZ 3JD0 3JD2 3JD3 3JD4
• EMDBエントリー: 6630 6631 6632 6633 6634 6635
• 分子名称: Glutamate dehydrogenase 1, mitochondrial, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE (2 entities in total)
• 機能のキーワード: glutamate metabolism, mitochondria, oxidoreductase
• 由来する生物種: Bos taurus (bovine)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 342798.84

構造登録者

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. (登録日: 2016-03-28, 公開日: 2016-04-27, 最終更新日: 2025-06-11)

主引用文献

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

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: 27036132
DOI: 10.1124/mol.116.103382

実験手法

ELECTRON MICROSCOPY (3.3 Å)