4DKL

Crystal structure of the mu-opioid receptor bound to a morphinan antagonist


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.235 

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This is version 1.4 of the entry. See complete history


Literature

Crystal structure of the {mu}-opioid receptor bound to a morphinan antagonist.

Manglik, A.Kruse, A.C.Kobilka, T.S.Thian, F.S.Mathiesen, J.M.Sunahara, R.K.Pardo, L.Weis, W.I.Kobilka, B.K.Granier, S.

(2012) Nature 485: 321-326

  • DOI: https://doi.org/10.1038/nature10954
  • Primary Citation of Related Structures:  
    4DKL

  • PubMed Abstract: 

    Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled µ-opioid receptor (µ-OR) in the central nervous system. Here we describe the 2.8 Å crystal structure of the mouse µ-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the µ-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.


  • Organizational Affiliation

    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mu-type opioid receptor, lysozyme chimera464Mus musculusTequatrovirus T4Mutation(s): 3 
Gene Names: MorOprmOprm1E
EC: 3.2.1.17
Membrane Entity: Yes 
UniProt
Find proteins for P42866 (Mus musculus)
Explore P42866 
Go to UniProtKB:  P42866
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP00720P42866
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BF0
Query on BF0

Download Ideal Coordinates CCD File 
B [auth A]methyl 4-{[(5beta,6alpha)-17-(cyclopropylmethyl)-3,14-dihydroxy-4,5-epoxymorphinan-6-yl]amino}-4-oxobutanoate
C25 H32 N2 O6
PGIBGSVRAVGQMY-OIUZVZFJSA-N
CLR
Query on CLR

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O [auth A]CHOLESTEROL
C27 H46 O
HVYWMOMLDIMFJA-DPAQBDIFSA-N
MPG
Query on MPG

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P [auth A],
Q [auth A]
[(Z)-octadec-9-enyl] (2R)-2,3-bis(oxidanyl)propanoate
C21 H40 O4
JPJYKWFFJCWMPK-GDCKJWNLSA-N
1PE
Query on 1PE

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R [auth A]PENTAETHYLENE GLYCOL
C10 H22 O6
JLFNLZLINWHATN-UHFFFAOYSA-N
SO4
Query on SO4

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C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
CL
Query on CL

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S [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.235 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.882α = 90
b = 174.73β = 107.84
c = 68.353γ = 90
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: 2012-03-21
    Type: Initial release
  • Version 1.1: 2012-05-16
    Changes: Database references
  • Version 1.2: 2016-06-08
    Changes: Atomic model
  • Version 1.3: 2017-07-26
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description