2GPU

Estrogen Related Receptor-gamma ligand binding domain complexed with 4-hydroxy-tamoxifen


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation.

Wang, L.Zuercher, W.J.Consler, T.G.Lambert, M.H.Miller, A.B.Orband-Miller, L.A.McKee, D.D.Willson, T.M.Nolte, R.T.

(2006) J Biol Chem 281: 37773-37781

  • DOI: https://doi.org/10.1074/jbc.M608410200
  • Primary Citation of Related Structures:  
    2GP7, 2GPO, 2GPP, 2GPU, 2GPV

  • PubMed Abstract: 

    X-ray crystal structures of the ligand binding domain (LBD) of the estrogen-related receptor-gamma (ERRgamma) were determined that describe this receptor in three distinct states: unliganded, inverse agonist bound, and agonist bound. Two structures were solved for the unliganded state, the ERRgamma LBD alone, and in complex with a coregulator peptide representing a portion of receptor interacting protein 140 (RIP140). No significant differences were seen between these structures that both exhibited the conformation of ERRgamma seen in studies with other coactivators. Two structures were obtained describing the inverse agonist-bound state, the ERRgamma LBD with 4-hydroxytamoxifen (4-OHT), and the ERRgamma LBD with 4-OHT and a peptide representing a portion of the silencing mediator of retinoid and thyroid hormone action protein (SMRT). The 4-OHT structure was similar to other reported inverse agonist bound structures, showing reorientation of phenylalanine 435 and a displacement of the AF-2 helix relative to the unliganded structures with little other rearrangement occurring. No significant changes to the LBD appear to be induced by peptide binding with the addition of the SMRT peptide to the ERRgamma plus 4-OHT complex. The observed agonist-bound state contains the ERRgamma LBD, a ligand (GSK4716), and the RIP140 peptide and reveals an unexpected rearrangement of the phenol-binding residues. Thermal stability studies show that agonist binding leads to global stabilization of the ligand binding domain. In contrast to the conventional mechanism of nuclear receptor ligand activation, activation of ERRgamma by GSK4716 does not appear to involve a major rearrangement or significant stabilization of the C-terminal helix.


  • Organizational Affiliation

    Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina 27909, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Estrogen-related receptor gamma230Homo sapiensMutation(s): 0 
Gene Names: ESRRG
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 BindingDB:  2GPU 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: 1.70 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.180 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.01α = 90
b = 64.01β = 90
c = 138.23γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
AMoREphasing
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345data collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-09-26
    Type: Initial release
  • Version 1.1: 2007-10-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description