5u1x

Crystal structure of the ATP-gated P2X7 ion channel bound to allosteric antagonist JNJ47965567

spinqualitylabelsall models 5u1x, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5u1x is a 1 chain structure with sequence from Ailuropoda melanoleuca. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.201Å Ligands: 7RV, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G1M6C4_AILME Receptor for ATP that acts as a ligand-gated ion channel.[RuleBase:RU000681] Publication Abstract from PubMed The P2X7 receptor is a non-selective cation channel activated by extracellular adenosine triphosphate (ATP). Chronic activation of P2X7 underlies many health problems such as pathologic pain, yet we lack effective antagonists due to poorly understood mechanisms of inhibition. Here we present crystal structures of a mammalian P2X7 receptor complexed with five structurally-unrelated antagonists. Unexpectedly, these drugs all bind to an allosteric site distinct from the ATP-binding pocket in a groove formed between two neighboring subunits. This novel drug-binding pocket accommodates a diversity of small molecules mainly through hydrophobic interactions. Functional assays propose that these compounds allosterically prevent narrowing of the drug-binding pocket and the turret-like architecture during channel opening, which is consistent with a site of action distal to the ATP-binding pocket. These novel mechanistic insights will facilitate the development of P2X7-specific drugs for treating human diseases. Structural basis for subtype-specific inhibition of the P2X7 receptor.,Karasawa A, Kawate T Elife. 2016 Dec 9;5. pii: e22153. doi: 10.7554/eLife.22153. PMID:27935479 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

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