4DLD

Crystal structure of the GluK1 ligand-binding domain (S1S2) in complex with the antagonist (S)-2-amino-3-(2-(2-carboxyethyl)-5-chloro-4-nitrophenyl)propionic acid at 2.0 A resolution

4DLD の概要

• エントリーDOI: 10.2210/pdb4dld/pdb
• 関連するPDBエントリー: 3TZA
• 分子名称: Glutamate receptor, ionotropic kainate 1, (S)-2-amino-3-(2-(2-carboxyethyl)-5-chloro-4-nitrophenyl)propionic acid, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: ionotropic glutamate receptor, glutamate, membrane, membrane 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: P22756
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59073.90

構造登録者

Venskutonyte, R.,Frydenvang, K.,Kastrup, J.S. (登録日: 2012-02-06, 公開日: 2012-10-10, 最終更新日: 2024-10-30)

主引用文献

Venskutonyte, R.,Frydenvang, K.,Valades, E.A.,Szymanska, E.,Johansen, T.N.,Kastrup, J.S.,Pickering, D.S.
Structural and pharmacological characterization of phenylalanine-based AMPA receptor antagonists at kainate receptors
Chemmedchem, 7:1793-1798, 2012

PubMed Abstract: Continued efforts into the discovery of ligands that target ionotropic glutamate receptors (iGluRs) are important for studies of the physiological roles of the various iGluR subtypes as well as for the search for drugs that can be used in the treatment of diseases of the central nervous system. A new series of phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors. Herein we report our studies of these compounds at the kainate receptors GluK1-3. Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not bind GluK2. The crystal structure of the most potent compound in the ligand binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2, due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a domain closure similar to that observed in GluK1 structures with partial agonists.

PubMed: 22407805
DOI: 10.1002/cmdc.201100599

実験手法

X-RAY DIFFRACTION (2 Å)