View source for 4s0v


==Crystal structure of the human OX2 orexin receptor bound to the insomnia drug Suvorexant==
<StructureSection load='4s0v' size='340' side='right'caption='[[4s0v]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4s0v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Pyrococcus_abyssi_GE5 Pyrococcus abyssi GE5]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4rnb 4rnb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S0V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S0V 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=SUV:[(7R)-4-(5-CHLORO-1,3-BENZOXAZOL-2-YL)-7-METHYL-1,4-DIAZEPAN-1-YL][5-METHYL-2-(2H-1,2,3-TRIAZOL-2-YL)PHENYL]METHANONE'>SUV</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=4s0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0v OCA], [https://pdbe.org/4s0v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s0v RCSB], [https://www.ebi.ac.uk/pdbsum/4s0v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0v ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9V2J8_PYRAB Q9V2J8_PYRAB] [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 ==
The orexin (also known as hypocretin) G protein-coupled receptors (GPCRs) respond to orexin neuropeptides in the central nervous system to regulate sleep and other behavioural functions in humans. Defects in orexin signalling are responsible for the human diseases of narcolepsy and cataplexy; inhibition of orexin receptors is an effective therapy for insomnia. The human OX2 receptor (OX2R) belongs to the beta branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant. Here, using lipid-mediated crystallization and protein engineering with a novel fusion chimaera, we solved the structure of the human OX2R bound to suvorexant at 2.5 A resolution. The structure reveals how suvorexant adopts a pi-stacked horseshoe-like conformation and binds to the receptor deep in the orthosteric pocket, stabilizing a network of extracellular salt bridges and blocking transmembrane helix motions necessary for activation. Computational docking suggests how other classes of synthetic antagonists may interact with the receptor at a similar position in an analogous pi-stacked fashion. Elucidation of the molecular architecture of the human OX2R expands our understanding of peptidergic GPCR ligand recognition and will aid further efforts to modulate orexin signalling for therapeutic ends.

Crystal structure of the human OX orexin receptor bound to the insomnia drug suvorexant.,Yin J, Mobarec JC, Kolb P, Rosenbaum DM Nature. 2014 Dec 22. doi: 10.1038/nature14035. PMID:25533960<ref>PMID:25533960</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4s0v" 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: Pyrococcus abyssi GE5]]
[[Category: Kolb P]]
[[Category: Mobarec JC]]
[[Category: Rosenbaum DM]]
[[Category: Yin J]]