7vod: Difference between revisions
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New page: '''Unreleased structure''' The entry 7vod is ON HOLD Authors: Chen, Z., Fan, L., Wang, H., Yu, J., Lu, D., Qi, J., Nie, F., Luo, Z., Liu, Z., Cheng, J., Wang, S. Description: Crystal s... |
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==Crystal structure of 5-HT2AR in complex with cariprazine== | |||
<StructureSection load='7vod' size='340' side='right'caption='[[7vod]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VOD 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]] 3.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7RU:3-[4-[2-[4-[2,3-bis(chloranyl)phenyl]piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethyl-urea'>7RU</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></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=7vod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vod OCA], [https://pdbe.org/7vod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vod RCSB], [https://www.ebi.ac.uk/pdbsum/7vod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vod ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Partial agonist activity at the dopamine D2 receptor (DRD2) is a key feature of third-generation antipsychotics (TGAs). However, TGAs also act as antagonists or weak partial agonists to the serotonin (5-hydroxytryptamine; 5-HT) 2A receptor (5-HT2AR). Here we present the crystal structures of aripiprazole- and cariprazine-bound human 5-HT2AR. Both TGAs adopt an unexpected 'upside-down' pose in the 5-HT2AR binding pocket, with secondary pharmacophores inserted in a similar way to a 'bolt'. This insight into the binding modes of TGAs offered a structural mechanism underlying their varied partial efficacies at 5-HT2AR and DRD2. These structures enabled the design of a partial agonist at DRD2/3 and 5-HT1AR with negligible 5-HT2AR binding that displayed potent antipsychotic-like activity without motor side effects in mice. This TGA lead also had antidepressant-like effects and improved cognitive performance in mouse models via 5-HT1AR. This work indicates that 5-HT2AR affinity is a dispensable contributor to the therapeutic actions of TGAs. | |||
Structure-based design of a novel third-generation antipsychotic drug lead with potential antidepressant properties.,Chen Z, Fan L, Wang H, Yu J, Lu D, Qi J, Nie F, Luo Z, Liu Z, Cheng J, Wang S Nat Neurosci. 2021 Dec 9. pii: 10.1038/s41593-021-00971-w. doi:, 10.1038/s41593-021-00971-w. PMID:34887590<ref>PMID:34887590</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7vod" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Fan | ==See Also== | ||
[[Category: Liu | *[[5-hydroxytryptamine receptor 3D structures|5-hydroxytryptamine receptor 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Wang | [[Category: Large Structures]] | ||
[[Category: | [[Category: Chen Z]] | ||
[[Category: | [[Category: Cheng J]] | ||
[[Category: Fan L]] | |||
[[Category: Liu Z]] | |||
[[Category: Lu D]] | |||
[[Category: Luo Z]] | |||
[[Category: Nie F]] | |||
[[Category: Qi J]] | |||
[[Category: Wang H]] | |||
[[Category: Wang S]] | |||
[[Category: Yu J]] | |||
Latest revision as of 14:08, 6 November 2024
Crystal structure of 5-HT2AR in complex with cariprazine
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