View source for 9bpc


==Cryo-EM structure of P2X3 receptor in complex with camlipixant==
<StructureSection load='9bpc' size='340' side='right'caption='[[9bpc]], [[Resolution|resolution]] 3.44&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bpc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Canis_lupus Canis lupus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BPC 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]] 3.44&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AQX:methyl+(2~{S})-2-[[2-[2,6-bis(fluoranyl)-4-(methylcarbamoyl)phenyl]-7-methyl-imidazo[1,2-a]pyridin-3-yl]methyl]morpholine-4-carboxylate'>A1AQX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9bpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bpc OCA], [https://pdbe.org/9bpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bpc RCSB], [https://www.ebi.ac.uk/pdbsum/9bpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bpc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A8I3S575_CANLF A0A8I3S575_CANLF] Receptor for ATP that acts as a ligand-gated ion channel.[PIRNR:PIRNR005713][RuleBase:RU000681]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ATP-activated P2X3 receptors play a pivotal role in chronic cough, affecting more than 10% of the population. Despite the challenges posed by the highly conserved structure of P2X receptors, efforts to develop selective drugs targeting P2X3 have led to the development of camlipixant, a potent, selective P2X3 antagonist. However, the mechanisms of receptor desensitization, ion permeation, and structural basis of camlipixant binding to P2X3 remain unclear. Here, we report a cryo-EM structure of camlipixant-bound P2X3, revealing a previously undiscovered selective drug-binding site in the receptor. Our findings also demonstrate that conformational changes in the upper body domain, including the turret and camlipixant-binding pocket, play a critical role: turret opening facilitates P2X3 channel closure to a radius of 0.7 A, hindering cation transfer, whereas turret closure leads to channel opening. Structural and functional studies combined with molecular dynamics simulations provide a comprehensive understanding of camlipixant's selective inhibition of P2X3, offering a foundation for future drug development targeting this receptor.

Mechanistic insights into the selective targeting of P2X3 receptor by camlipixant antagonist.,Thach T, Dhanabalan K, Nandekar PP, Stauffer S, Heisler I, Alvarado S, Snyder J, Subramanian R J Biol Chem. 2025 Jan;301(1):108109. doi: 10.1016/j.jbc.2024.108109. Epub 2024 , Dec 18. PMID:39706278<ref>PMID:39706278</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bpc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Canis lupus]]
[[Category: Large Structures]]
[[Category: Subramanian R]]
[[Category: Thach T]]