4n6h

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'''Unreleased structure'''
 
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The entry 4n6h is ON HOLD
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==1.8 A Structure of the human delta opioid 7TM receptor (PSI Community Target)==
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<StructureSection load='4n6h' size='340' side='right'caption='[[4n6h]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4n6h]] is a 1 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=4N6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N6H FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EJ4:(4BS,8R,8AS,14BR)-7-(CYCLOPROPYLMETHYL)-5,6,7,8,14,14B-HEXAHYDRO-4,8-METHANO[1]BENZOFURO[2,3-A]PYRIDO[4,3-B]CARBAZOLE-1,8A(9H)-DIOL'>EJ4</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4n6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n6h OCA], [https://pdbe.org/4n6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n6h RCSB], [https://www.ebi.ac.uk/pdbsum/4n6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n6h ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/OPRD_HUMAN OPRD_HUMAN] G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.<ref>PMID:22184124</ref> <ref>PMID:7808419</ref> <ref>PMID:8201839</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Opioids represent widely prescribed and abused medications, although their signal transduction mechanisms are not well understood. Here we present the 1.8 A high-resolution crystal structure of the human delta-opioid receptor (delta-OR), revealing the presence and fundamental role of a sodium ion in mediating allosteric control of receptor functional selectivity and constitutive activity. The distinctive delta-OR sodium ion site architecture is centrally located in a polar interaction network in the seven-transmembrane bundle core, with the sodium ion stabilizing a reduced agonist affinity state, and thereby modulating signal transduction. Site-directed mutagenesis and functional studies reveal that changing the allosteric sodium site residue Asn 131 to an alanine or a valine augments constitutive beta-arrestin-mediated signalling. Asp95Ala, Asn310Ala and Asn314Ala mutations transform classical delta-opioid antagonists such as naltrindole into potent beta-arrestin-biased agonists. The data establish the molecular basis for allosteric sodium ion control in opioid signalling, revealing that sodium-coordinating residues act as 'efficacy switches' at a prototypic G-protein-coupled receptor.
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Authors: Fenalti, G., Giguere, P.M., Katritch, V., Huang, X.-P., Thompson, A.A., Han, G.W., Cherezov, V., Roth, B.L., Stevens, R.C., GPCR Network (GPCR)
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Molecular control of delta-opioid receptor signalling.,Fenalti G, Giguere PM, Katritch V, Huang XP, Thompson AA, Cherezov V, Roth BL, Stevens RC Nature. 2014 Feb 13;506(7487):191-6. doi: 10.1038/nature12944. Epub 2014 Jan 12. PMID:24413399<ref>PMID:24413399</ref>
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Description: 1.8 A Structure of the human delta opioid 7TM receptor
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4n6h" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Escherichia coli]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cherezov V]]
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[[Category: Fenalti G]]
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[[Category: Giguere PM]]
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[[Category: Han GW]]
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[[Category: Huang X-P]]
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[[Category: Katritch V]]
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[[Category: Roth BL]]
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[[Category: Stevens RC]]
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[[Category: Thompson AA]]

Current revision

1.8 A Structure of the human delta opioid 7TM receptor (PSI Community Target)

PDB ID 4n6h

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