8AR7

Bovine glutamate dehydrogenase in ternary complex with the allosteric activators ADP and leucine

8AR7 の概要

• エントリーDOI: 10.2210/pdb8ar7/pdb
• 分子名称: Glutamate dehydrogenase (NAD(P)(+)), ADENOSINE-5'-DIPHOSPHATE, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: glutamate dehydrogenase, allosteric regulator, adp, leucine, cytosolic protein
• 由来する生物種: Bos taurus (cattle)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 373875.79

構造登録者

Aleshin, V.A.,Bellinzoni, M. (登録日: 2022-08-15, 公開日: 2022-10-05, 最終更新日: 2024-01-31)

主引用文献

Aleshin, V.A.,Bunik, V.I.,Bruch, E.M.,Bellinzoni, M.
Structural Basis for the Binding of Allosteric Activators Leucine and ADP to Mammalian Glutamate Dehydrogenase.
Int J Mol Sci, 23:-, 2022

PubMed Abstract: Glutamate dehydrogenase (GDH) plays a key role in the metabolism of glutamate, an important compound at a cross-road of carbon and nitrogen metabolism and a relevant neurotransmitter. Despite being one of the first discovered allosteric enzymes, GDH still poses challenges for structural characterization of its allosteric sites. Only the structures with ADP, and at low (3.5 Å) resolution, are available for mammalian GDH complexes with allosteric activators. Here, we aim at deciphering a structural basis for the GDH allosteric activation using bovine GDH as a model. For the first time, we report a mammalian GDH structure in a ternary complex with the activators leucine and ADP, co-crystallized with potassium ion, resolved to 2.45 Å. An improved 2.4-angstrom resolution of the GDH complex with ADP is also presented. The ternary complex with leucine and ADP differs from the binary complex with ADP by the conformation of GDH C-terminus, involved in the leucine binding and subunit interactions. The potassium site, identified in this work, may mediate interactions between the leucine and ADP binding sites. Our data provide novel insights into the mechanisms of GDH activation by leucine and ADP, linked to the enzyme regulation by (de)acetylation.

PubMed: 36232607
DOI: 10.3390/ijms231911306

実験手法

X-RAY DIFFRACTION (2.448 Å)