Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	P2X receptors exhibit at least three modes of allosteric antagonism.
Journal, issue, pages	Sci Adv, Vol. 10, Issue 40, Page eado5084, Year 2024
Publish date	Oct 4, 2024
Authors	Adam C Oken / Ismayn A Ditter / Nicolas E Lisi / Ipsita Krishnamurthy / Michael H Godsey / Steven E Mansoor /
PubMed Abstract	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.
External links	Sci Adv / PubMed:39365862 / PubMed Central
Methods	EM (single particle)
Resolution	2.18 - 2.69 Å
Structure data	41571 8tr6 EMDB-41571, PDB-8tr6: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist A438079 Method: EM (single particle) / Resolution: 2.18 Å 41572 8tr7 EMDB-41572, PDB-8tr7: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist A839977 Method: EM (single particle) / Resolution: 2.53 Å 41573 8tr8 EMDB-41573, PDB-8tr8: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist AZD9056 Method: EM (single particle) / Resolution: 2.21 Å 41575 8tra EMDB-41575, PDB-8tra: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist GSK1482160 Method: EM (single particle) / Resolution: 2.41 Å 41576 8trb EMDB-41576, PDB-8trb: Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist JNJ47965567 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 2.69 Å
Chemicals	ChemComp, No image ChemComp-KE3: Unknown entry ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying moleculeYM ChemComp-ZN: Unknown entry ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-PLM: PALMITIC ACID ChemComp-NA: Unknown entry ChemComp-HOH: WATER ChemComp, No image ChemComp-KDU: Unknown entry ChemComp, No image ChemComp-KEI: Unknown entry ChemComp, No image ChemComp-KF0: Unknown entry ChemComp-7RV: N-{[4-(4-phenylpiperazin-1-yl)oxan-4-yl]methyl}-2-(phenylsulfanyl)pyridine-3-carboxamide ChemComp, No image ChemComp-KFM*: Unknown entry
Source	rattus (rat)
Keywords	MEMBRANE PROTEIN / Ion Channel / Ligand-gate Ion Channel / P2X Receptor / Allosteric Antagonist / High-Affinity Agonist