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| <StructureSection load='7wc4' size='340' side='right'caption='[[7wc4]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='7wc4' size='340' side='right'caption='[[7wc4]], [[Resolution|resolution]] 3.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7wc4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WC4 FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WC4 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=SRO:SEROTONIN'>SRO</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=SRO:SEROTONIN'>SRO</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=7wc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wc4 OCA], [https://pdbe.org/7wc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wc4 RCSB], [https://www.ebi.ac.uk/pdbsum/7wc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wc4 ProSAT]</span></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=7wc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wc4 OCA], [https://pdbe.org/7wc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wc4 RCSB], [https://www.ebi.ac.uk/pdbsum/7wc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wc4 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function ==
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| [[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>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Drugs that target the human serotonin 2A receptor (5-HT2AR) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HT2AR complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d-lysergic acid diethylamide (LSD), as well as the endogenous neurotransmitter serotonin and the nonhallucinogenic psychedelic analog lisuride. Serotonin and psilocin display a second binding mode in addition to the canonical mode, which enabled the design of the psychedelic IHCH-7113 (a substructure of antipsychotic lumateperone) and several 5-HT2AR beta-arrestin-biased agonists that displayed antidepressant-like activity in mice but without hallucinogenic effects. The 5-HT2AR complex structures presented herein and the resulting insights provide a solid foundation for the structure-based design of safe and effective nonhallucinogenic psychedelic analogs with therapeutic effects.
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| Structure-based discovery of nonhallucinogenic psychedelic analogs.,Cao D, Yu J, Wang H, Luo Z, Liu X, He L, Qi J, Fan L, Tang L, Chen Z, Li J, Cheng J, Wang S Science. 2022 Jan 28;375(6579):403-411. doi: 10.1126/science.abl8615. Epub 2022, Jan 27. PMID:35084960<ref>PMID:35084960</ref>
| | ==See Also== |
| | | *[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7wc4" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Cao, D]] | | [[Category: Cao D]] |
| [[Category: Chen, Z]] | | [[Category: Chen Z]] |
| [[Category: Cheng, J]] | | [[Category: Cheng J]] |
| [[Category: Fan, L]] | | [[Category: Fan L]] |
| [[Category: He, L]] | | [[Category: He L]] |
| [[Category: Li, J]] | | [[Category: Li J]] |
| [[Category: Liu, X]] | | [[Category: Liu X]] |
| [[Category: Luo, Z]] | | [[Category: Luo Z]] |
| [[Category: Qi, J]] | | [[Category: Qi J]] |
| [[Category: Tang, L]] | | [[Category: Tang L]] |
| [[Category: Wang, H]] | | [[Category: Wang H]] |
| [[Category: Wang, S]] | | [[Category: Wang S]] |
| [[Category: Yu, J]] | | [[Category: Yu J]] |
| [[Category: 5-ht]]
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| [[Category: Membrane protein]]
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| [[Category: Serotonin]]
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| [[Category: Serotonin 2a receptor]]
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