4FAT

Ligand-binding domain of GluA2 (flip) ionotropic glutamate receptor in complex with an allosteric modulator

4FAT の概要

• エントリーDOI: 10.2210/pdb4fat/pdb
• 分子名称: Glutamate receptor 2, GLUTAMIC ACID, 2-({[4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}amino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide, ... (7 entities in total)
• 機能のキーワード: transport protein, ion channel, chimera protein, membrane protein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P19491
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30390.70

構造登録者

Maclean, J.K.F.,Kazemier, B. (登録日: 2012-05-22, 公開日: 2012-07-11, 最終更新日: 2024-11-20)

主引用文献

Harms, J.E.,Benveniste, M.,Maclean, J.K.,Partin, K.M.,Jamieson, C.
Functional analysis of a novel positive allosteric modulator of AMPA receptors derived from a structure-based drug design strategy.
Neuropharmacology, 64:45-52, 2013

PubMed Abstract: Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket. Here, we describe the electrophysiological properties of a new chemotype derived from a structure-based drug design strategy (SBDD), which makes similar receptor interactions compared to previously reported classes of modulator. This pyrazole amide derivative, JAMI1001A, with a promising developability profile, efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

PubMed: 22735771
DOI: 10.1016/j.neuropharm.2012.06.008

実験手法

X-RAY DIFFRACTION (1.4 Å)