2P7Z

Estrogen Related Receptor Gamma in complex with 4-hydroxy-tamoxifen


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.213 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural determination of estrogen-related receptor gamma in the presence of phenol derivative compounds.

Abad, M.C.Askari, H.O'Neill, J.Klinger, A.L.Milligan, C.Lewandowski, F.Springer, B.Spurlino, J.Rentzeperis, D.

(2008) J Steroid Biochem Mol Biol 108: 44-54

  • DOI: https://doi.org/10.1016/j.jsbmb.2007.06.006
  • Primary Citation of Related Structures:  
    2P7A, 2P7G, 2P7Z

  • PubMed Abstract: 

    We screened the ligand-binding domain of estrogen-related receptor (ERR) gamma in ThermoFluor, in an effort to develop chemical tools and decipher the biology of this orphan nuclear receptor. Several ligands were found to stabilize thermodynamically the protein. Amongst the ligands were bisphenol A (BPA) and 4-chloro-3-methyl phenol (ClCH3Ph). These ligands were further characterized and found to be competitive for 4-hydroxytamoxifen (4OHT) binding, a known reported antagonist ligand for ERRgamma, but functionally they did not enhance or disrupt affinity of the receptor for co-activator peptides. The preservation of the constitutive active conformation of the receptor in the presence of these two ligands was confirmed upon the determination of the co-crystal structures. The structures of BPA and ClCH3Ph were determined to a resolution of 2.1 and 2.3A, respectively, and the antagonist 4OHT was refined to 2.5A resolution. In the presence of BPA and ClCH3Ph the receptor maintained the transcriptional active conformation as reported previously for the apo-protein in the presence of a co-activator peptide fragment. In addition the ERRgamma-BPA structure identifies an interaction between the phenolic-OH and the side chain of N346. The preservation of the constitutive active conformation of the receptor in the presence of the small phenol compounds suggest that the biological activity of the receptor might be regulated by a natural occurring ligand.


  • Organizational Affiliation

    Johnson & Johnson Pharmaceuticals Research and Development, 665 Stockton Drive, Exton, PA 19341, USA. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Estrogen-related receptor gamma251Homo sapiensMutation(s): 0 
Gene Names: ESRRGERR3ERRG2KIAA0832NR3B3
UniProt & NIH Common Fund Data Resources
Find proteins for P62508 (Homo sapiens)
Explore P62508 
Go to UniProtKB:  P62508
PHAROS:  P62508
GTEx:  ENSG00000196482 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62508
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
OHT
Query on OHT

Download Ideal Coordinates CCD File 
B [auth A]4-HYDROXYTAMOXIFEN
C26 H29 N O2
TXUZVZSFRXZGTL-QPLCGJKRSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
OHT PDBBind:  2P7Z Kd: 262 (nM) from 1 assay(s)
BindingDB:  2P7Z IC50: min: 10.3, max: 1350 (nM) from 4 assay(s)
EC50: 15 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.213 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.99α = 90
b = 63.99β = 90
c = 137.952γ = 90
Software Package:
Software NamePurpose
CNSrefinement
PDB_EXTRACTdata extraction
PROTEUM PLUSdata collection
SAINTdata reduction
SCALAdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2008-02-26 
  • Deposition Author(s): Abad, M.C.

Revision History  (Full details and data files)

  • Version 1.0: 2008-02-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations
  • Version 1.3: 2024-04-03
    Changes: Refinement description