View source for 8fsp


==Full-length mouse 5-HT3A receptor in complex with SMP100, open-like==
<StructureSection load='8fsp' size='340' side='right'caption='[[8fsp]], [[Resolution|resolution]] 3.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fsp]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FSP 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]] 3.79&#8491;</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=Y82:5-[(1R,3S,4R)-1-azabicyclo[2.2.2]octan-3-yl]-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indazol-6-one'>Y82</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=8fsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fsp OCA], [https://pdbe.org/8fsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fsp RCSB], [https://www.ebi.ac.uk/pdbsum/8fsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fsp ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hyperactivity of serotonin 3 receptors (5-HT(3)R) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity competitive antagonists, are used in the treatment of these conditions. Although generally effective for chemotherapy-induced nausea and vomiting, the use of setrons for treating irritable bowel syndrome has been impaired by adverse side effects. Partial agonists are now being considered as an alternative strategy, with potentially less severe side effects than full antagonists. However, a structural understanding of how these ligands work is lacking. Here, we present high-resolution cryogenic electron microscopy structures of the mouse 5-HT(3A)R in complex with partial agonists (SMP-100 and ALB-148471) captured in pre-activated and open-like conformational states. Molecular dynamics simulations were used to assess the stability of drug-binding poses and interactions with the receptor over time. Together, these studies reveal mechanisms for the functional differences between orthosteric partial agonists, full agonists and antagonists of the 5-HT(3A)R.

Structural basis for partial agonism in 5-HT(3A) receptors.,Felt K, Stauffer M, Salas-Estrada L, Guzzo PR, Xie D, Huang J, Filizola M, Chakrapani S Nat Struct Mol Biol. 2024 Apr;31(4):598-609. doi: 10.1038/s41594-023-01140-2. , Epub 2024 Jan 4. PMID:38177669<ref>PMID:38177669</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fsp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Chakrapani S]]
[[Category: Felt KC]]