View source for 4ea3


==Structure of the N/OFQ Opioid Receptor in Complex with a Peptide Mimetic==
<StructureSection load='4ea3' size='340' side='right'caption='[[4ea3]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ea3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EA3 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]] 3.013&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NN:1-BENZYL-N-[3-(1H,3H-SPIRO[2-BENZOFURAN-1,4-PIPERIDIN]-1-YL)PROPYL]-D-PROLINAMIDE'>0NN</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLB:(2S)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLB</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=4ea3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ea3 OCA], [https://pdbe.org/4ea3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ea3 RCSB], [https://www.ebi.ac.uk/pdbsum/4ea3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ea3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/OPRX_HUMAN OPRX_HUMAN] G-protein coupled opioid receptor that functions as a receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.<ref>PMID:11238602</ref> <ref>PMID:12568343</ref> <ref>PMID:22596163</ref> <ref>PMID:23086955</ref> <ref>PMID:8137918</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Members of the opioid receptor family of G-protein-coupled receptors (GPCRs) are found throughout the peripheral and central nervous system, where they have key roles in nociception and analgesia. Unlike the 'classical' opioid receptors, delta, kappa and mu (delta-OR, kappa-OR and mu-OR), which were delineated by pharmacological criteria in the 1970s and 1980s, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP, also known as ORL-1) was discovered relatively recently by molecular cloning and characterization of an orphan GPCR. Although it shares high sequence similarity with classical opioid GPCR subtypes ( approximately 60%), NOP has a markedly distinct pharmacology, featuring activation by the endogenous peptide N/OFQ, and unique selectivity for exogenous ligands. Here we report the crystal structure of human NOP, solved in complex with the peptide mimetic antagonist compound-24 (C-24) (ref. 4), revealing atomic details of ligand-receptor recognition and selectivity. Compound-24 mimics the first four amino-terminal residues of the NOP-selective peptide antagonist UFP-101, a close derivative of N/OFQ, and provides important clues to the binding of these peptides. The X-ray structure also shows substantial conformational differences in the pocket regions between NOP and the classical opioid receptors kappa (ref. 5) and mu (ref. 6), and these are probably due to a small number of residues that vary between these receptors. The NOP-compound-24 structure explains the divergent selectivity profile of NOP and provides a new structural template for the design of NOP ligands.

Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic.,Thompson AA, Liu W, Chun E, Katritch V, Wu H, Vardy E, Huang XP, Trapella C, Guerrini R, Calo G, Roth BL, Cherezov V, Stevens RC Nature. 2012 May 16;485(7398):395-9. doi: 10.1038/nature11085. PMID:22596163<ref>PMID:22596163</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ea3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Opioid receptor|Opioid receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Calo G]]
[[Category: Cherezov V]]
[[Category: Chun E]]
[[Category: Guerrini R]]
[[Category: Huang XP]]
[[Category: Katritch V]]
[[Category: Liu W]]
[[Category: Roth BL]]
[[Category: Stevens RC]]
[[Category: Thompson AA]]
[[Category: Trapella C]]
[[Category: Vardy E]]
[[Category: Wu H]]