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	P2X receptors exhibit at least three modes of allosteric antagonism.
ジャーナル・号・ページ	Sci Adv, Vol. 10, Issue 40, Page eado5084, Year 2024
掲載日	2024年10月4日
著者	Adam C Oken / Ismayn A Ditter / Nicolas E Lisi / Ipsita Krishnamurthy / Michael H Godsey / Steven E Mansoor /
PubMed 要旨	P2X receptors are trimeric ion channels activated by adenosine triphosphate (ATP) that contribute to pathophysiological processes ranging from asthma to neuropathic pain and neurodegeneration. A ...P2X receptors are trimeric ion channels activated by adenosine triphosphate (ATP) that contribute to pathophysiological processes ranging from asthma to neuropathic pain and neurodegeneration. A number of small-molecule antagonists have been identified for these important pharmaceutical targets. However, the molecular pharmacology of P2X receptors is poorly understood because of the chemically disparate nature of antagonists and their differential actions on the seven constituent subtypes. Here, we report high-resolution cryo-electron microscopy structures of the homomeric rat P2X receptor bound to five previously known small-molecule allosteric antagonists and a sixth antagonist that we identify. Our structural, biophysical, and electrophysiological data define the molecular determinants of allosteric antagonism in this pharmacologically relevant receptor, revealing three distinct classes of antagonists that we call shallow, deep, and starfish. Starfish binders, exemplified by the previously unidentified antagonist methyl blue, represent a unique class of inhibitors with distinct functional properties that could be exploited to develop potent P2X ligands with substantial clinical impact.
リンク	Sci Adv / PubMed:39365862 / PubMed Central
手法	EM (単粒子)
解像度	2.18 - 2.69 Å
構造データ	41571 8tr6 EMDB-41571, PDB-8tr6: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist A438079 手法: EM (単粒子) / 解像度: 2.18 Å 41572 8tr7 EMDB-41572, PDB-8tr7: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist A839977 手法: EM (単粒子) / 解像度: 2.53 Å 41573 8tr8 EMDB-41573, PDB-8tr8: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist AZD9056 手法: EM (単粒子) / 解像度: 2.21 Å 41575 8tra EMDB-41575, PDB-8tra: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist GSK1482160 手法: EM (単粒子) / 解像度: 2.41 Å 41576 8trb EMDB-41576, PDB-8trb: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist JNJ47965567 手法: EM (単粒子) / 解像度: 2.36 Å 41582 8trk EMDB-41582, PDB-8trk: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist methyl blue 手法: EM (単粒子) / 解像度: 2.69 Å
化合物	化合物画像なし ChemComp-KE3: Unknown entry ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP / GDP, エネルギー貯蔵分子YM ChemComp-ZN: Unknown entry ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-PLM: PALMITIC ACID / パルミチン酸 ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-HOH: WATER 化合物画像なし ChemComp-KDU: Unknown entry 化合物画像なし ChemComp-KEI: Unknown entry 化合物画像なし ChemComp-KF0: Unknown entry ChemComp-7RV: N-{[4-(4-phenylpiperazin-1-yl)oxan-4-yl]methyl}-2-(phenylsulfanyl)pyridine-3-carboxamide 化合物画像なし ChemComp-KFM*: Unknown entry
由来	rattus (ネズミ)
キーワード	MEMBRANE PROTEIN / Ion Channel / Ligand-gate Ion Channel / P2X Receptor / Allosteric Antagonist / High-Affinity Agonist