EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Positive and negative allosteric modulation of GluK2 kainate receptors by BPAM344 and antiepileptic perampanel.
ジャーナル・号・ページ	Cell Rep, Vol. 42, Issue 2, Page 112124, Year 2023
掲載日	2023年2月21日
著者	Shanti Pal Gangwar / Laura Y Yen / Maria V Yelshanskaya / Alexander I Sobolevsky /
PubMed 要旨	Kainate receptors (KARs) are a subtype of ionotropic glutamate receptors that control synaptic transmission in the central nervous system and are implicated in neurological, psychiatric, and ...Kainate receptors (KARs) are a subtype of ionotropic glutamate receptors that control synaptic transmission in the central nervous system and are implicated in neurological, psychiatric, and neurodevelopmental disorders. Understanding the regulation of KAR function by small molecules is essential for exploring these receptors as drug targets. Here, we present cryoelectron microscopy (cryo-EM) structures of KAR GluK2 in complex with the positive allosteric modulator BPAM344, competitive antagonist DNQX, and negative allosteric modulator, antiepileptic drug perampanel. Our structures show that two BPAM344 molecules bind per ligand-binding domain dimer interface. In the absence of an agonist or in the presence of DNQX, BPAM344 stabilizes GluK2 in the closed state. The closed state is also stabilized by perampanel, which binds to the ion channel extracellular collar sites located in two out of four GluK2 subunits. The molecular mechanisms of positive and negative allosteric modulation of KAR provide a guide for developing new therapeutic strategies.
リンク	Cell Rep / PubMed:36857176 / PubMed Central
手法	EM (単粒子)
解像度	3.03 - 3.96 Å
構造データ	29515 8fwq EMDB-29515, PDB-8fwq: Structure of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 手法: EM (単粒子) / 解像度: 3.96 Å 29516 8fwr EMDB-29516, PDB-8fwr: Structure of the amino-terminal domain of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 手法: EM (単粒子) / 解像度: 3.1 Å 29517 8fws EMDB-29517, PDB-8fws: Structure of the ligand-binding and transmembrane domains of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 手法: EM (単粒子) / 解像度: 3.23 Å 29518 8fwt EMDB-29518, PDB-8fwt: Structure of the amino terminal domain of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and competitive antagonist DNQX 手法: EM (単粒子) / 解像度: 3.09 Å 29519 8fwu EMDB-29519, PDB-8fwu: Structure of the ligand-binding and transmembrane domains of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and competitive antagonist DNQX 手法: EM (単粒子) / 解像度: 3.18 Å 29520 8fwv EMDB-29520, PDB-8fwv: Structure of the amino-terminal domain of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and noncompetitive inhibitor perampanel 手法: EM (単粒子) / 解像度: 3.03 Å 29521 8fww EMDB-29521, PDB-8fww: Structure of the ligand-binding and transmembrane domains of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and noncompetitive inhibitor perampanel 手法: EM (単粒子) / 解像度: 3.1 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-2J9: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide / 3,4-ジヒドロ-4-シクロプロピル-7-フルオロ-2H-1,2,4-ベンゾチアジアジン1,1-ジオキシド ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM ChemComp-CL: Unknown entry / クロリド ChemComp-DNQ: 6,7-DINITROQUINOXALINE-2,3-DIONE / アンタゴニストYM ChemComp-HOH: WATER ChemComp-6ZP: 2-(6'-oxo-1'-phenyl[1',6'-dihydro[2,3'-bipyridine]]-5'-yl)benzonitrile / ペランパネル / 薬剤*YM
由来	rattus norvegicus (ドブネズミ)
キーワード	MEMBRANE PROTEIN / ion channel / iGluR / Kainate receptor / positive allosteric modulator / DNQX / Perampanel