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8bla
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 8bla is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Human serotonin 5-HT3A receptor in complex with vortioxetine (detergent, ECD only, active/distorted conformation)== | |
| + | <StructureSection load='8bla' size='340' side='right'caption='[[8bla]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8bla]] 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=8BLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BLA 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]] 3.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=VTX:Vortioxetine'>VTX</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=8bla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bla OCA], [https://pdbe.org/8bla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bla RCSB], [https://www.ebi.ac.uk/pdbsum/8bla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bla ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/5HT3A_HUMAN 5HT3A_HUMAN] Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.<ref>PMID:10521471</ref> <ref>PMID:12867984</ref> <ref>PMID:17392525</ref> <ref>PMID:9950429</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Vortioxetine (VTX) is a recently approved antidepressant that targets a variety of serotonin receptors. Here, we investigate the drug's molecular mechanism of operation at the serotonin 5-HT(3) receptor (5-HT(3)R), which features two properties: VTX acts differently on rodent and human 5-HT(3)R, and VTX appears to suppress any subsequent response to agonists. Using a combination of cryo-EM, electrophysiology, voltage-clamp fluorometry and molecular dynamics, we show that VTX stabilizes a resting inhibited state of the mouse 5-HT(3)R and an agonist-bound-like state of human 5-HT(3)R, in line with the functional profile of the drug. We report four human 5-HT(3)R structures and show that the human receptor transmembrane domain is intrinsically fragile. We also explain the lack of recovery after VTX administration via a membrane partition mechanism. | ||
| - | + | Structural determinants for activity of the antidepressant vortioxetine at human and rodent 5-HT(3) receptors.,Lopez-Sanchez U, Munro LJ, Ladefoged LK, Pedersen AJ, Brun CC, Lyngby SM, Baud D, Juillan-Binard C, Pedersen MG, Lummis SCR, Bang-Andersen B, Schiott B, Chipot C, Schoehn G, Neyton J, Dehez F, Nury H, Kristensen AS Nat Struct Mol Biol. 2024 May 2. doi: 10.1038/s41594-024-01282-x. PMID:38698207<ref>PMID:38698207</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8bla" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lopez-Sanchez U]] | ||
| + | [[Category: Nury H]] | ||
Current revision
Human serotonin 5-HT3A receptor in complex with vortioxetine (detergent, ECD only, active/distorted conformation)
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