4NF8

Crystal structure of GluN1/GluN2A ligand-binding domain in complex with glycine and glutamate in PEG2000MME

4NF8 の概要

• エントリーDOI: 10.2210/pdb4nf8/pdb
• 関連するPDBエントリー: 4NF4 4NF5 4NF6
• 分子名称: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2A, GLYCINE, ... (5 entities in total)
• 機能のキーワード: receptor, glycine and glutamate, transport protein
• 由来する生物種: Rattus norvegicus (rat); 詳細
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : P35439 Q00959
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65347.53

構造登録者

Jespersen, A.,Tajima, N.,Furukawa, H. (登録日: 2013-10-30, 公開日: 2014-03-12, 最終更新日: 2024-10-16)

主引用文献

Jespersen, A.,Tajima, N.,Fernandez-Cuervo, G.,Garnier-Amblard, E.C.,Furukawa, H.
Structural Insights into Competitive Antagonism in NMDA Receptors.
Neuron, 81:366-378, 2014

PubMed Abstract: There has been a great level of enthusiasm to downregulate overactive N-methyl-D-aspartate (NMDA) receptors to protect neurons from excitotoxicity. NMDA receptors play pivotal roles in basic brain development and functions as well as in neurological disorders and diseases. However, mechanistic understanding of antagonism in NMDA receptors is limited due to complete lack of antagonist-bound structures for the L-glutamate-binding GluN2 subunits. Here, we report the crystal structures of GluN1/GluN2A NMDA receptor ligand-binding domain (LBD) heterodimers in complex with GluN1- and GluN2-targeting antagonists. The crystal structures reveal that the antagonists, D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and 1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA), have discrete binding modes and mechanisms for opening of the bilobed architecture of GluN2A LBD compared to the agonist-bound form. The current study shows distinct ways by which the conformations of NMDA receptor LBDs may be controlled and coupled to receptor inhibition and provides possible strategies to develop therapeutic compounds with higher subtype-specificity.

PubMed: 24462099
DOI: 10.1016/j.neuron.2013.11.033

実験手法

X-RAY DIFFRACTION (1.856 Å)