1QKN

RAT OESTROGEN RECEPTOR BETA LIGAND-BINDING DOMAIN IN COMPLEX WITH ANTAGONIST RALOXIFENE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.204 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure of the Ligand-Binding Domain of Oestrogen Receptor Beta in the Presence of a Partial Agonist and a Full Antagonist

Pike, A.C.W.Brzozowski, A.M.Hubbard, R.E.Bonn, T.Thorsell, A.-G.Engstrom, O.Ljunggren, J.Gustaffson, J.-A.Carlquist, M.

(1999) EMBO J 18: 4608

  • DOI: https://doi.org/10.1093/emboj/18.17.4608
  • Primary Citation of Related Structures:  
    1QKM, 1QKN

  • PubMed Abstract: 

    Oestrogens exert their physiological effects through two receptor subtypes. Here we report the three-dimensional structure of the oestrogen receptor beta isoform (ERbeta) ligand-binding domain (LBD) in the presence of the phyto-oestrogen genistein and the antagonist raloxifene. The overall structure of ERbeta-LBD is very similar to that previously reported for ERalpha. Each ligand interacts with a unique set of residues within the hormone-binding cavity and induces a distinct orientation in the AF-2 helix (H12). The bulky side chain of raloxifene protrudes from the cavity and physically prevents the alignment of H12 over the bound ligand. In contrast, genistein is completely buried within the hydrophobic core of the protein and binds in a manner similar to that observed for ER's endogenous hormone, 17beta-oestradiol. However, in the ERbeta-genistein complex, H12 does not adopt the distinctive 'agonist' position but, instead, lies in a similar orientation to that induced by ER antagonists. Such a sub-optimal alignment of the transactivation helix is consistent with genistein's partial agonist character in ERbeta and demonstrates how ER's transcriptional response to certain bound ligands is attenuated.


  • Organizational Affiliation

    Structural Biology Laboratory, Chemistry Department, University of York, York YO10 5DD, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ESTROGEN RECEPTOR BETA255Rattus norvegicusMutation(s): 0 
Gene Names: OESTROGEN RECEPTOR BETA
UniProt
Find proteins for Q62986 (Rattus norvegicus)
Explore Q62986 
Go to UniProtKB:  Q62986
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ62986
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
RAL BindingDB:  1QKN Ki: min: 2.74, max: 23 (nM) from 5 assay(s)
IC50: min: 0.2, max: 557 (nM) from 19 assay(s)
EC50: min: 4.32, max: 341 (nM) from 2 assay(s)
PDBBind:  1QKN IC50: 3.4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.204 
  • Space Group: P 41 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.55α = 90
b = 67.55β = 90
c = 148.2γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-07-28
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-07-24
    Changes: Data collection
  • Version 1.4: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description