6pt2: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
<table><tr><td colspan='2'>[[6pt2]] is a 4 chain structure with sequence from [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=6PT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PT2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6pt2]] is a 4 chain structure with sequence from [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=6PT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PT2 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]] 2.8Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DI7:2,6-DIMETHYL-L-TYROSINE'>DI7</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=OXJ:1-[3,5-bis(trifluoromethyl)phenyl]-N- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DI7:2,6-DIMETHYL-L-TYROSINE'>DI7</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=OXJ:1-[3,5-bis(trifluoromethyl)phenyl]-~{N}-methyl-methanamine'>OXJ</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</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=6pt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pt2 OCA], [https://pdbe.org/6pt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pt2 RCSB], [https://www.ebi.ac.uk/pdbsum/6pt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pt2 ProSAT]</span></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=6pt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pt2 OCA], [https://pdbe.org/6pt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pt2 RCSB], [https://www.ebi.ac.uk/pdbsum/6pt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pt2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/OPRD_HUMAN OPRD_HUMAN] G-protein coupled receptor that functions as 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> | [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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Latest revision as of 16:00, 6 November 2024
Crystal structure of the active delta opioid receptor in complex with the peptide agonist KGCHM07Crystal structure of the active delta opioid receptor in complex with the peptide agonist KGCHM07
Structural highlights
FunctionOPRD_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.[1] [2] [3] Publication Abstract from PubMedSelective 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||