3S2V

Crystal Structure of the Ligand Binding Domain of GluK1 in Complex with an Antagonist (S)-1-(2'-Amino-2'-carboxyethyl)-3-[(2-carboxythien-3-yl)methyl]thieno[3,4-d]pyrimidin-2,4-dione at 2.5 A Resolution

3S2V の概要

• エントリーDOI: 10.2210/pdb3s2v/pdb
• 関連するPDBエントリー: 2F34
• 分子名称: Glutamate receptor, ionotropic kainate 1, (S)-1-(2'-AMINO-2'-CARBOXYETHYL)-3-[(2-CARBOXYTHIEN-3-YL)METHYL]THIENO[3,4-D]PYRIMIDIN-2,4-DIONE, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: antagonist, ionotropic glutamate receptor, 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: 59515.56

構造登録者

Venskutonyte, R.,Frydenvang, K.,Kastrup, J.S. (登録日: 2011-05-17, 公開日: 2011-06-22, 最終更新日: 2024-11-20)

主引用文献

Venskutonyte, R.,Butini, S.,Coccone, S.S.,Gemma, S.,Brindisi, M.,Kumar, V.,Guarino, E.,Maramai, S.,Valenti, S.,Amir, A.,Valades, E.A.,Frydenvang, K.,Kastrup, J.S.,Novellino, E.,Campiani, G.,Pickering, D.S.
Selective kainate receptor (GluK1) ligands structurally based upon 1H-cyclopentapyrimidin-2,4(1H,3H)-dione: synthesis, molecular modeling, and pharmacological and biostructural characterization.
J.Med.Chem., 54:4793-4805, 2011

PubMed Abstract: The physiological function of kainate receptors (GluK1-GluK5) in the central nervous system is not fully understood yet. With the aim of developing potent and selective GluK1 ligands, we have synthesized a series of new thiophene-based GluK1 agonists (6a-c) and antagonists (7a-d). Pharmacological evaluation revealed that they are selective for the GluK1 subunit, with 7b being the most subtype-selective ligand reported to date (GluK1 vs GluK3). The antagonist 7a was cocrystallized with the GluK1 ligand binding domain, and an X-ray crystallographic analysis revealed the largest flexibility in GluK1 ligand binding domain opening upon binding of a ligand seen to date. The results provide new insights into the molecular mechanism of GluK1 receptor ligand binding and pave the way to the development of new tool compounds for studying kainate receptor function.

PubMed: 21619066
DOI: 10.1021/jm2004078

実験手法

X-RAY DIFFRACTION (2.5 Å)