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8jv7
From Proteopedia
(Difference between revisions)
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| - | ==Cryo-EM | + | ==Cryo-EM structure of the panda P2X7 receptor in complex with PPADS== |
<StructureSection load='8jv7' size='340' side='right'caption='[[8jv7]], [[Resolution|resolution]] 3.60Å' scene=''> | <StructureSection load='8jv7' size='340' side='right'caption='[[8jv7]], [[Resolution|resolution]] 3.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8jv7]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Ailuropoda_melanoleuca Ailuropoda melanoleuca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JV7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8jv7]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Ailuropoda_melanoleuca Ailuropoda melanoleuca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JV7 FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UO6:4-[(E)-[4-methanoyl-6-methyl-5-oxidanyl-3-(phosphonooxymethyl)pyridin-2-yl]diazenyl]benzene-1,3-disulfonic+acid'>UO6</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UO6:4-[(~{E})-[4-methanoyl-6-methyl-5-oxidanyl-3-(phosphonooxymethyl)pyridin-2-yl]diazenyl]benzene-1,3-disulfonic+acid'>UO6</scene></td></tr> |
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8jv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jv7 OCA], [https://pdbe.org/8jv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jv7 RCSB], [https://www.ebi.ac.uk/pdbsum/8jv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jv7 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8jv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jv7 OCA], [https://pdbe.org/8jv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jv7 RCSB], [https://www.ebi.ac.uk/pdbsum/8jv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jv7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/G1M6C4_AILME G1M6C4_AILME] Receptor for ATP that acts as a ligand-gated ion channel.[RuleBase:RU000681] |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | P2X receptors are extracellular ATP-gated ion channels that form homo- or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery. We determined the cryogenic electron microscopy (cryo-EM) structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5'-phosphate derivatives, pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS) and pyridoxal phosphate-6-azophenyl-2',5'-disulfonic acid (PPADS), and performed structure-based mutational analysis by patch-clamp recording as well as molecular dynamics (MD) simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo- and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes. | ||
| + | |||
| + | Structural insights into the orthosteric inhibition of P2X receptors by non-ATP analog antagonists.,Sheng D, Yue CX, Jin F, Wang Y, Ichikawa M, Yu Y, Guo CR, Hattori M Elife. 2024 Apr 5;12:RP92829. doi: 10.7554/eLife.92829. PMID:38578670<ref>PMID:38578670</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8jv7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Cryo-EM structure of the panda P2X7 receptor in complex with PPADS
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