6dry
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==Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor== | ==Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor== | ||
| - | <StructureSection load='6dry' size='340' side='right' caption='[[6dry]], [[Resolution|resolution]] 2.92Å' scene=''> | + | <StructureSection load='6dry' size='340' side='right'caption='[[6dry]], [[Resolution|resolution]] 2.92Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6dry]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DRY OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6dry]] 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=6DRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DRY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=H8D:( | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.918Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=H8D:(6~{a}~{R},9~{R})-7-methyl-~{N}-[(2~{S})-1-oxidanylbutan-2-yl]-6,6~{a},8,9-tetrahydro-4~{H}-indolo[4,3-fg]quinoline-9-carboxamide'>H8D</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6dry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dry OCA], [https://pdbe.org/6dry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dry RCSB], [https://www.ebi.ac.uk/pdbsum/6dry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dry ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [[ | + | [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/5HT2B_HUMAN 5HT2B_HUMAN] This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Plays a role in the regulation of impulsive behavior. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Serotonin (5-hydroxytryptamine; 5-HT) receptors modulate a variety of physiological processes ranging from perception, cognition and emotion to vascular and smooth muscle contraction, platelet aggregation, gastrointestinal function and reproduction. Drugs that interact with 5-HT receptors effectively treat diseases as diverse as migraine headaches, depression and obesity. Here we present four structures of a prototypical serotonin receptor-the human 5-HT2B receptor-in complex with chemically and pharmacologically diverse drugs, including methysergide, methylergonovine, lisuride and LY266097. A detailed analysis of these structures complemented by comprehensive interrogation of signaling illuminated key structural determinants essential for activation. Additional structure-guided mutagenesis experiments revealed binding pocket residues that were essential for agonist-mediated biased signaling and beta-arrestin2 translocation. Given the importance of 5-HT receptors for a large number of therapeutic indications, insights derived from these studies should accelerate the design of safer and more effective medications. | ||
| + | |||
| + | Structural determinants of 5-HT2B receptor activation and biased agonism.,McCorvy JD, Wacker D, Wang S, Agegnehu B, Liu J, Lansu K, Tribo AR, Olsen RHJ, Che T, Jin J, Roth BL Nat Struct Mol Biol. 2018 Aug 20. pii: 10.1038/s41594-018-0116-7. doi:, 10.1038/s41594-018-0116-7. PMID:30127358<ref>PMID:30127358</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6dry" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Escherichia coli]] |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Agegnehu B]] |
| - | [[Category: | + | [[Category: Che T]] |
| - | [[Category: | + | [[Category: Jin J]] |
| - | [[Category: | + | [[Category: Lansu K]] |
| - | [[Category: | + | [[Category: Liu J]] |
| - | [[Category: | + | [[Category: McCorvy JD]] |
| - | [[Category: | + | [[Category: Olsen RHJ]] |
| - | [[Category: | + | [[Category: Roth BL]] |
| - | [[Category: | + | [[Category: Tribo AR]] |
| - | [[Category: | + | [[Category: Wacker D]] |
| - | [[Category: | + | [[Category: Wang S]] |
| - | + | ||
Current revision
Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor
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Categories: Escherichia coli | Homo sapiens | Large Structures | Agegnehu B | Che T | Jin J | Lansu K | Liu J | McCorvy JD | Olsen RHJ | Roth BL | Tribo AR | Wacker D | Wang S
