8TRB
Cryo-EM structure of the rat P2X7 receptor in complex with the allosteric antagonist JNJ47965567
This is a non-PDB format compatible entry.
Summary for 8TRB
| Entry DOI | 10.2210/pdb8trb/pdb |
| Related | 8TR6 8TR7 8TR8 8TRA 8TRK |
| EMDB information | 41571 41572 41573 41575 41576 41582 |
| Descriptor | P2X purinoceptor 7, N-{[4-(4-phenylpiperazin-1-yl)oxan-4-yl]methyl}-2-(phenylsulfanyl)pyridine-3-carboxamide, GUANOSINE-5'-DIPHOSPHATE, ... (8 entities in total) |
| Functional Keywords | membrane protein, ion channel, ligand-gate ion channel, p2x receptor, allosteric antagonist, high-affinity agonist |
| Biological source | Rattus More |
| Total number of polymer chains | 3 |
| Total formula weight | 213801.97 |
| Authors | Oken, A.C.,Ditter, I.A.,Lisi, N.E.,Krishnamurthy, I.,McCarthy, A.E.,Godsey, M.H.,Mansoor, S.E. (deposition date: 2023-08-09, release date: 2024-10-16, Last modification date: 2024-11-13) |
| Primary citation | Oken, A.C.,Ditter, I.A.,Lisi, N.E.,Krishnamurthy, I.,Godsey, M.H.,Mansoor, S.E. P2X 7 receptors exhibit at least three modes of allosteric antagonism. Sci Adv, 10:eado5084-eado5084, 2024 Cited by 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 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. PubMed: 39365862DOI: 10.1126/sciadv.ado5084 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.36 Å) |
Structure validation
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