4rwd

From Proteopedia

(Difference between revisions)

Current revision

XFEL structure of the human delta opioid receptor in complex with a bifunctional peptide

Structural highlights

4rwd is a 4 chain structure with sequence from Escherichia coli, Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

C562_ECOLX Electron-transport protein of unknown 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

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^[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
↑ 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. Structural basis for bifunctional peptide recognition at human delta-opioid receptor. Nat Struct Mol Biol. 2015 Mar;22(3):265-8. doi: 10.1038/nsmb.2965. Epub 2015 Feb , 16. PMID:25686086 doi:http://dx.doi.org/10.1038/nsmb.2965

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rwd"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4rwd]] 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=4RWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RWD FirstGlance]. <br>
-</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=PRD_001256:bifunctional+peptide'>PRD_001256</scene></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]] 2.7&#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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</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=4rwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rwd OCA], [https://pdbe.org/4rwd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rwd RCSB], [https://www.ebi.ac.uk/pdbsum/4rwd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rwd 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 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/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 ==

4rwd

From Proteopedia

Current revision

XFEL structure of the human delta opioid receptor in complex with a bifunctional peptide

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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