8f7s

From Proteopedia

(Difference between revisions)

Revision as of 07:14, 21 November 2024

Gi bound delta-opioid receptor in complex with deltorphin

Structural highlights

8f7s is a 8 chain structure with sequence from Bos taurus, Homo sapiens, Phyllomedusa and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid system contains four opioid receptors (muOR, deltaOR, kappaOR, and NOPR) and a set of related endogenous opioid peptides (EOPs), which show distinct selectivity toward their respective opioid receptors (ORs). Despite being key to the development of safer analgesics, the mechanisms of molecular recognition and selectivity of EOPs to ORs remain unclear. Here, we systematically characterize the binding of EOPs to ORs and present five structures of EOP-OR-G(i) complexes, including beta-endorphin- and endomorphin-bound muOR, deltorphin-bound deltaOR, dynorphin-bound kappaOR, and nociceptin-bound NOPR. These structures, supported by biochemical results, uncover the specific recognition and selectivity of opioid peptides and the conserved mechanism of opioid receptor activation. These results provide a structural framework to facilitate rational design of safer opioid drugs for pain relief.

Structures of the entire human opioid receptor family.,Wang Y, Zhuang Y, DiBerto JF, Zhou XE, Schmitz GP, Yuan Q, Jain MK, Liu W, Melcher K, Jiang Y, Roth BL, Xu HE Cell. 2023 Jan 19;186(2):413-427.e17. doi: 10.1016/j.cell.2022.12.026. Epub 2023 , Jan 12. PMID:36638794^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Leskela TT, Lackman JJ, Vierimaa MM, Kobayashi H, Bouvier M, Petaja-Repo UE. Cys-27 variant of human delta-opioid receptor modulates maturation and cell surface delivery of Phe-27 variant via heteromerization. J Biol Chem. 2012 Feb 10;287(7):5008-20. doi: 10.1074/jbc.M111.305656. Epub 2011 , Dec 19. PMID:22184124 doi:http://dx.doi.org/10.1074/jbc.M111.305656
↑ Simonin F, Befort K, Gaveriaux-Ruff C, Matthes H, Nappey V, Lannes B, Micheletti G, Kieffer B. The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain. Mol Pharmacol. 1994 Dec;46(6):1015-21. PMID:7808419
↑ Knapp RJ, Malatynska E, Fang L, Li X, Babin E, Nguyen M, Santoro G, Varga EV, Hruby VJ, Roeske WR, et al.. Identification of a human delta opioid receptor: cloning and expression. Life Sci. 1994;54(25):PL463-9. PMID:8201839
↑ Wang Y, Zhuang Y, DiBerto JF, Zhou XE, Schmitz GP, Yuan Q, Jain MK, Liu W, Melcher K, Jiang Y, Roth BL, Xu HE. Structures of the entire human opioid receptor family. Cell. 2023 Jan 19;186(2):413-427.e17. PMID:36638794 doi:10.1016/j.cell.2022.12.026

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8f7s"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8f7s]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Phyllomedusa Phyllomedusa] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8F7S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F7S FirstGlance]. <br>
-</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=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</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=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=8f7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f7s OCA], [https://pdbe.org/8f7s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f7s RCSB], [https://www.ebi.ac.uk/pdbsum/8f7s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f7s ProSAT]</span></td></tr>
 </table>
 == 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;">
+== Publication Abstract from PubMed ==
+Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid system contains four opioid receptors (muOR, deltaOR, kappaOR, and NOPR) and a set of related endogenous opioid peptides (EOPs), which show distinct selectivity toward their respective opioid receptors (ORs). Despite being key to the development of safer analgesics, the mechanisms of molecular recognition and selectivity of EOPs to ORs remain unclear. Here, we systematically characterize the binding of EOPs to ORs and present five structures of EOP-OR-G(i) complexes, including beta-endorphin- and endomorphin-bound muOR, deltorphin-bound deltaOR, dynorphin-bound kappaOR, and nociceptin-bound NOPR. These structures, supported by biochemical results, uncover the specific recognition and selectivity of opioid peptides and the conserved mechanism of opioid receptor activation. These results provide a structural framework to facilitate rational design of safer opioid drugs for pain relief.
+Structures of the entire human opioid receptor family.,Wang Y, Zhuang Y, DiBerto JF, Zhou XE, Schmitz GP, Yuan Q, Jain MK, Liu W, Melcher K, Jiang Y, Roth BL, Xu HE Cell. 2023 Jan 19;186(2):413-427.e17. doi: 10.1016/j.cell.2022.12.026. Epub 2023 , Jan 12. PMID:36638794<ref>PMID:36638794</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 8f7s" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Opioid receptor|Opioid receptor]]
+*[[Transducin 3D structures|Transducin 3D structures]]
 == References ==
 <references/>

8f7s

From Proteopedia

Revision as of 07:14, 21 November 2024

Gi bound delta-opioid receptor in complex with deltorphin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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