View source for 6bqg


==Crystal structure of 5-HT2C in complex with ergotamine==
<StructureSection load='6bqg' size='340' side='right'caption='[[6bqg]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bqg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BQG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[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=ERM:ERGOTAMINE'>ERM</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</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=6bqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bqg OCA], [https://pdbe.org/6bqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bqg RCSB], [https://www.ebi.ac.uk/pdbsum/6bqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bqg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/5HT2C_HUMAN 5HT2C_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.<ref>PMID:12970106</ref> <ref>PMID:18703043</ref> <ref>PMID:19057895</ref> <ref>PMID:7895773</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Drugs frequently require interactions with multiple targets-via a process known as polypharmacology-to achieve their therapeutic actions. Currently, drugs targeting several serotonin receptors, including the 5-HT2C receptor, are useful for treating obesity, drug abuse, and schizophrenia. The competing challenges of developing selective 5-HT2C receptor ligands or creating drugs with a defined polypharmacological profile, especially aimed at G protein-coupled receptors (GPCRs), remain extremely difficult. Here, we solved two structures of the 5-HT2C receptor in complex with the highly promiscuous agonist ergotamine and the 5-HT2A-C receptor-selective inverse agonist ritanserin at resolutions of 3.0 A and 2.7 A, respectively. We analyzed their respective binding poses to provide mechanistic insights into their receptor recognition and opposing pharmacological actions. This study investigates the structural basis of polypharmacology at canonical GPCRs and illustrates how understanding characteristic patterns of ligand-receptor interaction and activation may ultimately facilitate drug design at multiple GPCRs.

5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology.,Peng Y, McCorvy JD, Harpsoe K, Lansu K, Yuan S, Popov P, Qu L, Pu M, Che T, Nikolajsen LF, Huang XP, Wu Y, Shen L, Bjorn-Yoshimoto WE, Ding K, Wacker D, Han GW, Cheng J, Katritch V, Jensen AA, Hanson MA, Zhao S, Gloriam DE, Roth BL, Stevens RC, Liu ZJ Cell. 2018 Feb 8;172(4):719-730.e14. doi: 10.1016/j.cell.2018.01.001. Epub 2018, Feb 1. PMID:29398112<ref>PMID:29398112</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6bqg" style="background-color:#fffaf0;"></div>

==See Also==
*[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bjorn-Yoshimoto WE]]
[[Category: Che T]]
[[Category: Cheng J]]
[[Category: Ding K]]
[[Category: Gloriam DE]]
[[Category: Han GW]]
[[Category: Hanson MA]]
[[Category: Harpsoe K]]
[[Category: Huang XP]]
[[Category: Jensen AA]]
[[Category: Katritch V]]
[[Category: Lansu K]]
[[Category: Liu Z]]
[[Category: McCorvy JD]]
[[Category: Nikolajse LF]]
[[Category: Peng Y]]
[[Category: Popov P]]
[[Category: Pu M]]
[[Category: Qu L]]
[[Category: Roth BL]]
[[Category: Shen L]]
[[Category: Stevens RC]]
[[Category: Wacker D]]
[[Category: Wu Y]]
[[Category: Yuan S]]
[[Category: Zhao S]]