View source for 6pt3


==Crystal structure of the active delta opioid receptor in complex with the small molecule agonist DPI-287==
<StructureSection load='6pt3' size='340' side='right'caption='[[6pt3]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pt3]] is a 2 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=6PT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PT3 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OWY:4-[(R)-[(2S,5R)-4-benzyl-2,5-dimethylpiperazin-1-yl](3-hydroxyphenyl)methyl]-N,N-diethylbenzamide'>OWY</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=6pt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pt3 OCA], [https://pdbe.org/6pt3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pt3 RCSB], [https://www.ebi.ac.uk/pdbsum/6pt3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pt3 ProSAT]</span></td></tr>
</table>
== 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 ==
Selective activation of the delta-opioid receptor (DOP) has great potential for the treatment of chronic pain, benefitting from ancillary anxiolytic and antidepressant-like effects. Moreover, DOP agonists show reduced adverse effects as compared to mu-opioid receptor (MOP) agonists that are in the spotlight of the current "opioid crisis." Here, we report the first crystal structures of the DOP in an activated state, in complex with two relevant and structurally diverse agonists: the potent opioid agonist peptide KGCHM07 and the small-molecule agonist DPI-287 at 2.8 and 3.3 A resolution, respectively. Our study identifies key determinants for agonist recognition, receptor activation, and DOP selectivity, revealing crucial differences between both agonist scaffolds. Our findings provide the first investigation into atomic-scale agonist binding at the DOP, supported by site-directed mutagenesis and pharmacological characterization. These structures will underpin the future structure-based development of DOP agonists for an improved pain treatment with fewer adverse effects.

Elucidating the active delta-opioid receptor crystal structure with peptide and small-molecule agonists.,Claff T, Yu J, Blais V, Patel N, Martin C, Wu L, Han GW, Holleran BJ, Van der Poorten O, White KL, Hanson MA, Sarret P, Gendron L, Cherezov V, Katritch V, Ballet S, Liu ZJ, Muller CE, Stevens RC Sci Adv. 2019 Nov 27;5(11):eaax9115. doi: 10.1126/sciadv.aax9115. eCollection, 2019 Nov. PMID:31807708<ref>PMID:31807708</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6pt3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Opioid receptor|Opioid receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ballet S]]
[[Category: Blais V]]
[[Category: Cherezov V]]
[[Category: Claff T]]
[[Category: Gendron L]]
[[Category: Han GW]]
[[Category: Hanson MA]]
[[Category: Holleran BJ]]
[[Category: Katritch V]]
[[Category: Liu Z]]
[[Category: Martin C]]
[[Category: Muller CE]]
[[Category: Patel N]]
[[Category: Sarret P]]
[[Category: Stevens RC]]
[[Category: Van der Poorten O]]
[[Category: Wu L]]
[[Category: Yu J]]