1S9P

crystal structure of the ligand-binding domain of the estrogen-related receptor gamma in complex with diethylstilbestrol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.13 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.226 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural Basis for the Deactivation of the Estrogen-related Receptor {gamma} by Diethylstilbestrol or 4-Hydroxytamoxifen and Determinants of Selectivity.

Greschik, H.Flaig, R.Renaud, J.P.Moras, D.

(2004) J Biol Chem 279: 33639-33646

  • DOI: https://doi.org/10.1074/jbc.M402195200
  • Primary Citation of Related Structures:  
    1S9P, 1S9Q, 1TFC, 1VJB

  • PubMed Abstract: 

    The estrogen-related receptor (ERR) gamma behaves as a constitutive activator of transcription. Although no natural ligand is known, ERRgamma is deactivated by the estrogen receptor (ER) agonist diethylstilbestrol and the selective ER modulator 4-hydroxytamoxifen but does not significantly respond to estradiol or raloxifene. Here we report the crystal structures of the ERRgamma ligand binding domain (LBD) complexed with diethylstilbestrol or 4-hydroxytamoxifen. Antagonist binding to ERRgamma results in a rotation of the side chain of Phe-435 that partially fills the cavity of the apoLBD. The new rotamer of Phe-435 displaces the "activation helix" (helix 12) from the agonist position observed in the absence of ligand. In contrast to the complexes of the ERalpha LBD with 4-hydroxytamoxifen or raloxifene, helix 12 of antagonist-bound ERRgamma does not occupy the coactivator groove but appears to be completely dissociated from the LBD body. Comparison of the ligand-bound LBDs of ERRgamma and ERalpha reveals small but significant differences in the architecture of the ligand binding pockets that result in a slightly shifted binding position of diethylstilbestrol and a small rotation of 4-hydroxytamoxifen in the cavity of ERRgamma relative to ERalpha. Our results provide detailed molecular insight into the conformational changes occurring upon binding of synthetic antagonists to the constitutive orphan receptor ERRgamma and reveal structural differences with ERs that explain why ERRgamma does not bind estradiol or raloxifene and will help to design new selective antagonists.


  • Organizational Affiliation

    Département de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, B. P. 10142, 67404 Illkirch, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Estrogen-related receptor gamma
A, B, C, D
227Mus musculusMutation(s): 0 
Gene Names: ESRRGNR3B3ERRG2ERR3KIAA0832
UniProt
Find proteins for P62509 (Mus musculus)
Explore P62509 
Go to UniProtKB:  P62509
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62509
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.13 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.226 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.999α = 90
b = 77.46β = 97.55
c = 95.773γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data 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: 2004-06-08
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description