View source for 9arz


==Local refinement of 5-HT2AR bound to 2-bromo-LSD in complex with a mini-Gq protein and scFv16 obtained by cryo-electron microscopy (cryoEM)==
<StructureSection load='9arz' size='340' side='right'caption='[[9arz]], [[Resolution|resolution]] 3.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9arz]] 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=9ARZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ARZ 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]] 3.37&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AFU:2-bromo-N,N-diethyl-6-methyl-9,10-didehydroergoline-8beta-carboxamide'>A1AFU</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=9arz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9arz OCA], [https://pdbe.org/9arz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9arz RCSB], [https://www.ebi.ac.uk/pdbsum/9arz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9arz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/5HT2A_HUMAN 5HT2A_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors (PubMed:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538). Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores (PubMed:18703043, PubMed:28129538). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.<ref>PMID:1330647</ref> <ref>PMID:18297054</ref> <ref>PMID:18703043</ref> <ref>PMID:19057895</ref> <ref>PMID:21645528</ref> <ref>PMID:22300836</ref> <ref>PMID:28129538</ref>   (Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.<ref>PMID:24089568</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
There is currently a resurgence in exploring the utility of classical psychedelics to treat depression, addiction, anxiety disorders, cluster headaches, and many other neuropsychiatric disorders. A biological target of these compounds, and a hypothesized target for their therapeutic actions, is the 5-HT(2A) serotonin receptor. Here, we present 7 cryo-EM structures covering all major compound classes of psychedelic and non-psychedelic agonists, including a beta-arrestin-biased compound RS130-180. Identifying the molecular interactions between various psychedelics and the 5-HT(2A) receptor reveals both common and distinct motifs among the examined psychedelic chemotypes. These findings lead to a broader mechanistic understanding of 5-HT(2A) activation, which can catalyze the development of novel chemotypes with potential therapeutic utility and fewer side effects.

The structural diversity of psychedelic drug actions revealed.,Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, DiBerto JF, Krumm BE, Kapolka NJ, Kaniskan HU, Nichols DE, Jin J, Fay JF, Roth BL Nat Commun. 2025 Mar 19;16(1):2734. doi: 10.1038/s41467-025-57956-7. PMID:40108183<ref>PMID:40108183</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9arz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fay JF]]
[[Category: Gumpper RH]]
[[Category: Roth BL]]