View source for 7xrr


==Crystal structure of the human OX2R bound to the insomnia drug lemborexant.==
<StructureSection load='7xrr' size='340' side='right'caption='[[7xrr]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xrr]] 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=7XRR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XRR 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]] 2.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NRK:(1~{R},2~{S})-2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-~{N}-(5-fluoranylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropane-1-carboxamide'>NRK</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=7xrr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xrr OCA], [https://pdbe.org/7xrr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xrr RCSB], [https://www.ebi.ac.uk/pdbsum/7xrr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xrr 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 ==
Orexin receptors are a family of G protein-coupled receptors that consist of two subtypes: orexin-1 receptors (OX1Rs) and OX2Rs. They are expressed throughout the central nervous system and are involved in regulating the sleep-wake cycle. The development of antagonists to orexin receptors has become important in drug discovery because modulation of these receptors can lead to novel treatments for diseases related to the regulation of sleep and wakefulness, such as insomnia. In this study, we determined that the structure of OX2R bound to lemborexant, a dual orexin receptor antagonist (DORA), at 2.89 A resolution. Comparisons of kinetic and dynamic properties of DORAs based on structures and simulations suggest that the enthalpy of molecular binding to receptors and the entropy derived from intramolecular structure can be separately controlled. These results complement existing structural information and allow us to discuss the usefulness of pharmacophore models and target selectivity to OXRs.

Molecular basis for anti-insomnia drug design from structure of lemborexant-bound orexin 2 receptor.,Asada H, Im D, Hotta Y, Yasuda S, Murata T, Suno R, Iwata S Structure. 2022 Dec 1;30(12):1582-1589.e4. doi: 10.1016/j.str.2022.11.001. Epub , 2022 Nov 22. PMID:36417909<ref>PMID:36417909</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xrr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Orexin and Orexin receptor|Orexin and Orexin receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Asada H]]
[[Category: Im D]]
[[Category: Iwata S]]