View source for 8v6u


==5HT2AR-miniGq heterotrimer in complex with a novel agonist obtained from large scale docking==
<StructureSection load='8v6u' size='340' side='right'caption='[[8v6u]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8v6u]] is a 5 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=8V6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8V6U 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YEQ:4-{(3R)-1-[(1R)-1-(pyrimidin-2-yl)ethyl]piperidin-3-yl}phenol'>YEQ</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=8v6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8v6u OCA], [https://pdbe.org/8v6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8v6u RCSB], [https://www.ebi.ac.uk/pdbsum/8v6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8v6u 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 ==
AlphaFold2 (AF2) models have had wide impact, but they have had mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 models of the sigma2 and 5-HT2A receptors, testing hundreds of new molecules and comparing results to docking against the experimental structures. Hit rates were high and similar for the experimental and the AF2 structures, as were affinities. The success of docking against the AF2 models was achieved despite differences in orthosteric residue conformations versus the experimental structures. Determination of the cryo-electron microscopy structure for one of the more potent 5HT2A ligands from the AF2 docking revealed residue accommodations that resembled the AF2 prediction. AF2 models may sample conformations that differ from experimental structures but remain low energy and relevant for ligand discovery, extending the domain of structure-based ligand discovery.

AlphaFold2 structures guide prospective ligand discovery.,Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, Barros-Alvarez X, Sakamoto K, Kim Y, DiBerto J, Kim K, Glenn IS, Tummino TA, Huang S, Irwin JJ, Tarkhanova OO, Moroz Y, Skiniotis G, Kruse AC, Shoichet BK, Roth BL Science. 2024 May 16:eadn6354. doi: 10.1126/science.adn6354. PMID:38753765<ref>PMID:38753765</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8v6u" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gumpper RH]]
[[Category: Kapolka N]]
[[Category: Roth BL]]
[[Category: Skiniotis G]]
[[Category: Wang L]]