View source for 4rwa


==Synchrotron structure of the human delta opioid receptor in complex with a bifunctional peptide (PSI community target)==
<StructureSection load='4rwa' size='340' side='right'caption='[[4rwa]], [[Resolution|resolution]] 3.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rwa]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RWA 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]] 3.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DI7:2,6-DIMETHYL-L-TYROSINE'>DI7</scene>, <scene name='pdbligand=DI8:(3S)-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC+ACID'>DI8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=4rwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rwa OCA], [https://pdbe.org/4rwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rwa RCSB], [https://www.ebi.ac.uk/pdbsum/4rwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rwa 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/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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bifunctional mu- and delta-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human delta-OR bound to the bifunctional delta-OR antagonist and mu-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.

Structural basis for bifunctional peptide recognition at human delta-opioid receptor.,Fenalti G, Zatsepin NA, Betti C, Giguere P, Han GW, Ishchenko A, Liu W, Guillemyn K, Zhang H, James D, Wang D, Weierstall U, Spence JC, Boutet S, Messerschmidt M, Williams GJ, Gati C, Yefanov OM, White TA, Oberthuer D, Metz M, Yoon CH, Barty A, Chapman HN, Basu S, Coe J, Conrad CE, Fromme R, Fromme P, Tourwe D, Schiller PW, Roth BL, Ballet S, Katritch V, Stevens RC, Cherezov V Nat Struct Mol Biol. 2015 Mar;22(3):265-8. doi: 10.1038/nsmb.2965. Epub 2015 Feb , 16. PMID:25686086<ref>PMID:25686086</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4rwa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Ballet S]]
[[Category: Barty A]]
[[Category: Basu S]]
[[Category: Betti C]]
[[Category: Boutet S]]
[[Category: Chapman HN]]
[[Category: Cherezov V]]
[[Category: Coe J]]
[[Category: Conrad CE]]
[[Category: Fenalti G]]
[[Category: Fromme P]]
[[Category: Fromme R]]
[[Category: Gati C]]
[[Category: Giguere P]]
[[Category: Guillemyn K]]
[[Category: Han GW]]
[[Category: Ishchenko A]]
[[Category: James D]]
[[Category: Katritch V]]
[[Category: Liu W]]
[[Category: Messerschmidt M]]
[[Category: Metz M]]
[[Category: Oberthuer D]]
[[Category: Roth BL]]
[[Category: Schiller PW]]
[[Category: Spence JCH]]
[[Category: Stevens RC]]
[[Category: Tourwe D]]
[[Category: Wang D]]
[[Category: Weierstall U]]
[[Category: White TA]]
[[Category: Williams GJ]]
[[Category: Yefanov OM]]
[[Category: Yoon CH]]
[[Category: Zatsepin NA]]
[[Category: Zhang H]]