View source for 21ci


==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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 21ci" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mima M]]
[[Category: Mishima-Tsumagari C]]