9bpd: Difference between revisions
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==Cryo-EM structure of P2X3 receptor in complex with ATP:Mg2+== | |||
<StructureSection load='9bpd' size='340' side='right'caption='[[9bpd]], [[Resolution|resolution]] 3.63Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9bpd]] 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=9BPD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BPD 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]] 3.63Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=9bpd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bpd OCA], [https://pdbe.org/9bpd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bpd RCSB], [https://www.ebi.ac.uk/pdbsum/9bpd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bpd 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9bpd" style="background-color:#fffaf0;"></div> | ||
[[Category: Subramanian | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Canis lupus]] | |||
[[Category: Large Structures]] | |||
[[Category: Subramanian R]] | |||
[[Category: Thach T]] | |||
