21ci: Difference between revisions

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'''Unreleased structure'''


The entry 21ci is ON HOLD  until Paper Publication
==Crystal structure of human orexin type 2 receptor in complex with vornorexant==
<StructureSection load='21ci' size='340' side='right'caption='[[21ci]], [[Resolution|resolution]] 3.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[21ci]] is a 1 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=21CI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=21CI 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]] 3.29&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1MCY:[(2~{S})-2-[[3-(5-fluoranylpyridin-2-yl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-[5-methyl-2-(1,2,3-triazol-2-yl)phenyl]methanone'>A1MCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=21ci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=21ci OCA], [https://pdbe.org/21ci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=21ci RCSB], [https://www.ebi.ac.uk/pdbsum/21ci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=21ci ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OX2R_HUMAN OX2R_HUMAN] Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Insomnia is a widespread sleep disorder that significantly impairs quality of life and imposes a societal burden. Although benzodiazepines and Z-drugs are commonly used for treating insomnia, these drugs often have side effects, such as excessive muscle relaxation and dependency. The orexin signaling pathway has emerged as a promising therapeutic target for insomnia, with dual orexin receptor antagonists (DORAs) offering an alternative approach to treatment. To reduce the potential of these drugs for next-day residual effects, we developed vornorexant, a novel DORA with a high receptor affinity and a short elimination half-life. In this study, we investigated the molecular interactions of this drug with human orexin receptors through crystal structure analysis of its binding to orexin type 2 receptor (OX(2)R) and a docking simulation of the drug with orexin type 1 receptor (OX(1)R). The crystal structure of the OX(2)R-vornorexant complex revealed a conserved U-shaped conformation stabilized by hydrophobic and hydrogen-bonding interactions, including key contacts with Asn324, His350 and Pro131. OX(1)R-vornorexant docking simulations indicated a similar binding mode to OX(1)R, with no steric hindrance observed, supporting a balanced dual antagonism. These results provide a structural basis for the high-affinity dual antagonism of vornorexant and offer insights for the design of orexin receptor antagonists.


Authors: Mima, M., Mishima-Tsumagari, C.
Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors.,Mima M, Mishima-Tsumagari C, Sakata-Sakuta M, Iwaoka R, Iwamoto K Acta Crystallogr F Struct Biol Commun. 2026 Jun 1;82(Pt 6):201-207. doi: , 10.1107/S2053230X26003432. Epub 2026 Apr 30. PMID:42059114<ref>PMID:42059114</ref>


Description: Crystal structure of human orexin type 2 receptor in complex with vornorexant
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Mishima-Tsumagari, C]]
<div class="pdbe-citations 21ci" style="background-color:#fffaf0;"></div>
[[Category: Mima, M]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mima M]]
[[Category: Mishima-Tsumagari C]]
Retrieved from "https://proteopedia.org/21ci"