21ah: Difference between revisions

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'''Unreleased structure'''


The entry 21ah is ON HOLD  until 2027-12-04
==LY334370-bound serotonin 1F (5-HT1F) receptor==
<StructureSection load='21ah' size='340' side='right'caption='[[21ah]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[21ah]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=21AH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=21AH 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]] 3.18&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1E2G:4-fluoranyl-~{N}-[3-(1-methylpiperidin-4-yl)-1~{H}-indol-5-yl]benzamide'>A1E2G</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=21ah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=21ah OCA], [https://pdbe.org/21ah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=21ah RCSB], [https://www.ebi.ac.uk/pdbsum/21ah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=21ah ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/5HT1F_HUMAN 5HT1F_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:21422162, PubMed:34239069, PubMed:8380639, PubMed:8384716). Also functions as a receptor for various alkaloids and psychoactive substances (PubMed:21422162, PubMed:8380639, PubMed:8384716). Receptor for lasmiditan, a drug for the treatment of acute migraine (PubMed:34239069). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:34239069). HTR1F is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:34239069, PubMed:35610220).<ref>PMID:21422162</ref> <ref>PMID:34239069</ref> <ref>PMID:35610220</ref> <ref>PMID:8380639</ref> <ref>PMID:8384716</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 5-HT(1F) receptor is a serotonin receptor subtype highly expressed in trigeminal sensory neurons, where it modulates neuropeptide release and nociceptive signaling without inducing vasoconstriction. This makes it an important therapeutic target for migraine. LY334370 was developed as a first-generation selective 5-HT(1F)R agonist and demonstrated efficacy in clinical studies. However, the molecular mechanism underlying 5-HT(1F)R activation by LY334370 remains poorly understood. Here, we determined a 3.13 A cryo-EM structure of the LY334370-bound 5-HT(1F)R-miniGalpha(oA) complex. Combined with functional analyses, this structure delineates the molecular determinants underlying LY334370 recognition. Comparison with BRL54443 indicates that LY334370 selectivity for 5-HT(1F)R is driven by its optimal accommodation within the receptor-specific extended binding pocket. Furthermore, comparative analysis with the lasmiditan-bound 5-HT(1F)R-Galpha(i1) complex reveals distinct agonist binding modes and provides mechanistic insight into Galpha(i/o) subtype-specific coupling. Collectively, these findings elucidate the structural basis of 5-HT(1F)R activation, ligand selectivity, and G protein coupling, providing a structural framework for the rational design of safer and more effective anti-migraine drugs.


Authors:  
Structural basis of LY334370 recognition and selectivity at the 5-HT(1F) receptor.,Wang Y, Wang C, Cao C Biochem Biophys Res Commun. 2026 Mar 12;804:153313. doi: , 10.1016/j.bbrc.2026.153313. Epub 2026 Jan 21. PMID:41619505<ref>PMID:41619505</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 21ah" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao C]]
[[Category: Ji Z]]
[[Category: Wang Y]]
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