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5dhh

From Proteopedia

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Current revision

The crystal structure of nociceptin/orphanin FQ peptide receptor (NOP) in complex with SB-612111 (PSI Community Target)

Structural highlights

5dhh is a 2 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.004Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

C562_ECOLX Electron-transport protein of unknown function.OPRX_HUMAN G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Understanding the mechanism by which ligands affect receptor conformational equilibria is key in accelerating membrane protein structural biology. In the case of G protein-coupled receptors (GPCRs), we currently pursue a brute-force approach for identifying ligands that stabilize receptors and facilitate crystallogenesis. The nociceptin/orphanin FQ peptide receptor (NOP) is a member of the opioid receptor subfamily of GPCRs for which many structurally diverse ligands are available for screening. We observed that antagonist potency is correlated with a ligand's ability to induce receptor stability (Tm) and crystallogenesis. Using this screening strategy, we solved two structures of NOP in complex with top candidate ligands SB-612111 and C-35. Docking studies indicate that while potent, stabilizing antagonists strongly favor a single binding orientation, less potent ligands can adopt multiple binding modes, contributing to their low Tm values. These results suggest a mechanism for ligand-aided crystallogenesis whereby potent antagonists stabilize a single ligand-receptor conformational pair.

The Importance of Ligand-Receptor Conformational Pairs in Stabilization: Spotlight on the N/OFQ G Protein-Coupled Receptor.,Miller RL, Thompson AA, Trapella C, Guerrini R, Malfacini D, Patel N, Han GW, Cherezov V, Calo G, Katritch V, Stevens RC Structure. 2015 Oct 24. pii: S0969-2126(15)00407-4. doi:, 10.1016/j.str.2015.07.024. PMID:26526853^[6]

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

References

↑ Serhan CN, Fierro IM, Chiang N, Pouliot M. Cutting edge: nociceptin stimulates neutrophil chemotaxis and recruitment: inhibition by aspirin-triggered-15-epi-lipoxin A4. J Immunol. 2001 Mar 15;166(6):3650-4. doi: 10.4049/jimmunol.166.6.3650. PMID:11238602 doi:http://dx.doi.org/10.4049/jimmunol.166.6.3650
↑ Spampinato S, Di Toro R, Alessandri M, Murari G. Agonist-induced internalization and desensitization of the human nociceptin receptor expressed in CHO cells. Cell Mol Life Sci. 2002 Dec;59(12):2172-83. doi: 10.1007/s000180200016. PMID:12568343 doi:http://dx.doi.org/10.1007/s000180200016
↑ Thompson AA, Liu W, Chun E, Katritch V, Wu H, Vardy E, Huang XP, Trapella C, Guerrini R, Calo G, Roth BL, Cherezov V, Stevens RC. Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic. Nature. 2012 May 16;485(7398):395-9. doi: 10.1038/nature11085. PMID:22596163 doi:10.1038/nature11085
↑ Zhang NR, Planer W, Siuda ER, Zhao HC, Stickler L, Chang SD, Baird MA, Cao YQ, Bruchas MR. Serine 363 is required for nociceptin/orphanin FQ opioid receptor (NOPR) desensitization, internalization, and arrestin signaling. J Biol Chem. 2012 Dec 7;287(50):42019-30. doi: 10.1074/jbc.M112.405696. Epub 2012, Oct 19. PMID:23086955 doi:http://dx.doi.org/10.1074/jbc.M112.405696
↑ Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC. ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett. 1994 Mar 14;341(1):33-8. doi: 10.1016/0014-5793(94)80235-1. PMID:8137918 doi:http://dx.doi.org/10.1016/0014-5793(94)80235-1
↑ Miller RL, Thompson AA, Trapella C, Guerrini R, Malfacini D, Patel N, Han GW, Cherezov V, Calo G, Katritch V, Stevens RC. The Importance of Ligand-Receptor Conformational Pairs in Stabilization: Spotlight on the N/OFQ G Protein-Coupled Receptor. Structure. 2015 Oct 24. pii: S0969-2126(15)00407-4. doi:, 10.1016/j.str.2015.07.024. PMID:26526853 doi:http://dx.doi.org/10.1016/j.str.2015.07.024

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/5dhh"

@@ Line 1: / Line 1: @@
 ==The crystal structure of nociceptin/orphanin FQ peptide receptor (NOP) in complex with SB-612111 (PSI Community Target)==
-<StructureSection load='5dhh' size='340' side='right' caption='[[5dhh]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+<StructureSection load='5dhh' size='340' side='right'caption='[[5dhh]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5dhh]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DHH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5dhh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DHH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGW:(5S,7S)-7-{[4-(2,6-DICHLOROPHENYL)PIPERIDIN-1-YL]METHYL}-1-METHYL-6,7,8,9-TETRAHYDRO-5H-BENZO[7]ANNULEN-5-OL'>DGW</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.004&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ea3|4ea3]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGW:(5S,7S)-7-{[4-(2,6-DICHLOROPHENYL)PIPERIDIN-1-YL]METHYL}-1-METHYL-6,7,8,9-TETRAHYDRO-5H-BENZO[7]ANNULEN-5-OL'>DGW</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5dhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dhh OCA], [http://pdbe.org/5dhh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dhh RCSB], [http://www.ebi.ac.uk/pdbsum/5dhh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dhh 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=5dhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dhh OCA], [https://pdbe.org/5dhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dhh RCSB], [https://www.ebi.ac.uk/pdbsum/5dhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dhh ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX]] Electron-transport protein of unknown function.
+[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/OPRX_HUMAN OPRX_HUMAN] G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.<ref>PMID:11238602</ref> <ref>PMID:12568343</ref> <ref>PMID:22596163</ref> <ref>PMID:23086955</ref> <ref>PMID:8137918</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Calo, G]]
+[[Category: Escherichia coli]]
-[[Category: Cherezov, V]]
+[[Category: Homo sapiens]]
-[[Category: GPCR, GPCR Network]]
+[[Category: Large Structures]]
-[[Category: Guerrini, R]]
+[[Category: Calo G]]
-[[Category: Han, G W]]
+[[Category: Cherezov V]]
-[[Category: Katritch, V]]
+[[Category: Guerrini R]]
-[[Category: Malfacini, D]]
+[[Category: Han GW]]
-[[Category: Miller, R L]]
+[[Category: Katritch V]]
-[[Category: Patel, N]]
+[[Category: Malfacini D]]
-[[Category: Stevens, R C]]
+[[Category: Miller RL]]
-[[Category: Thompson, A A]]
+[[Category: Patel N]]
-[[Category: Trapella, C]]
+[[Category: Stevens RC]]
-[[Category: Bret]]
+[[Category: Thompson AA]]
-[[Category: G protein-coupled receptor]]
+[[Category: Trapella C]]
-[[Category: Gpcr]]
-[[Category: Gpcr network]]
-[[Category: Lipidic cubic phase]]
-[[Category: Membrane protein]]
-[[Category: N/ofq]]
-[[Category: Nociceptin/orphanin fq peptide receptor]]
-[[Category: Nop]]
-[[Category: Opioid receptor]]
-[[Category: Orl-1]]
-[[Category: Psi-biology]]
-[[Category: Psicnt-127]]
-[[Category: Receptor-ligand conformational pair]]
-[[Category: Signaling protein]]
-[[Category: Structural genomic]]

5dhh

From Proteopedia

Current revision

The crystal structure of nociceptin/orphanin FQ peptide receptor (NOP) in complex with SB-612111 (PSI Community Target)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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