4EJ4

Structure of the delta opioid receptor bound to naltrindole


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.252 
  • R-Value Observed: 0.255 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history


Literature

Structure of the delta opioid receptor bound to naltrindole

Granier, S.Manglik, A.Kruse, A.C.Kobilka, T.S.Thian, F.S.Weis, W.I.Kobilka, B.K.

(2012) Nature 485: 400-404

  • DOI: https://doi.org/10.1038/nature11111
  • Primary Citation of Related Structures:  
    4EJ4

  • PubMed Abstract: 

    The opioid receptor family comprises three members, the µ-, δ- and κ-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The δ-opioid receptor (δ-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the µ-OR and κ-OR have recently been solved. Here we report the crystal structure of the mouse δ-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the µ-OR and κ-OR, the δ-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the δ-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.


  • Organizational Affiliation

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Delta-type opioid receptor, Lysozyme chimera461Mus musculusTequatrovirus T4Mutation(s): 3 
Gene Names: Oprd1E
EC: 3.2.1.17
Membrane Entity: Yes 
UniProt
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Find proteins for P32300 (Mus musculus)
Explore P32300 
Go to UniProtKB:  P32300
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP00720P32300
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EJ4
Query on EJ4

Download Ideal Coordinates CCD File 
B [auth A](4bS,8R,8aS,14bR)-7-(cyclopropylmethyl)-5,6,7,8,14,14b-hexahydro-4,8-methano[1]benzofuro[2,3-a]pyrido[4,3-b]carbazole-1,8a(9H)-diol
C26 H26 N2 O3
WIYUZYBFCWCCQJ-IFKAHUTRSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EJ4 BindingDB:  4EJ4 Ki: min: 0.03, max: 2.63 (nM) from 14 assay(s)
IC50: min: 0.51, max: 0.72 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.252 
  • R-Value Observed: 0.255 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.278α = 90
b = 73.278β = 90
c = 266.653γ = 120
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-16
    Type: Initial release
  • Version 1.1: 2012-06-27
    Changes: Database references
  • Version 1.2: 2017-08-23
    Changes: Refinement description, Source and taxonomy
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2024-10-30
    Changes: Structure summary