3NSP

Crystal structure of tetrameric RXRalpha-LBD


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.308 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.226 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Danthron functions as a retinoic X receptor antagonist by stabilizing tetramers of the receptor.

Zhang, H.Zhou, R.Li, L.Chen, J.Chen, L.Li, C.Ding, H.Yu, L.Hu, L.Jiang, H.Shen, X.

(2011) J Biol Chem 286: 1868-1875

  • DOI: https://doi.org/10.1074/jbc.M110.166215
  • Primary Citation of Related Structures:  
    3NSP, 3NSQ

  • PubMed Abstract: 

    Retinoic X receptor (RXR) is a promising target for drug discovery against cancer and metabolic syndromes. Here, we identified a specific RXRα antagonist, danthron, from the traditional Chinese medicine rhubarb. Danthron repressed all tested RXRα-involved response element transcription, including the RXRE, PPRE, FXRE, and LXRE. Results from native PAGE and isothermal titration calorimetry (ITC)-based assays indicated that danthron bound to the tetrameric RXRα-LBD in a specific stoichimetric ratio, and such a binding could influence the corepressor SMRT affinity to the receptor. Additionally, a unique tetrameric structure of the apo-RXRα ligand-binding domain (LBD) was determined, which exhibited a larger tetramer interface and different ligand-binding pocket size compared with the one previously reported. Together with the biochemical and biophysical results, the determined crystal structure of danthron-soaked RXRα-LBD suggested a new mechanism for danthron antagonism to tetrameric RXRα. Moreover, the in vivo efficient improvement of insulin sensitivity by danthron was observed in diet-induced obese (DIO) mice. Thus, our findings were expected to supply new insights into the structural basis of RXRα antagonist for its further potential therapeutic application.


  • Organizational Affiliation

    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Retinoid X receptor, alpha
A, B
240Homo sapiensMutation(s): 0 
Gene Names: RXRANR2B1RP11-473E2.1-002hCG_18150
UniProt & NIH Common Fund Data Resources
Find proteins for P19793 (Homo sapiens)
Explore P19793 
Go to UniProtKB:  P19793
PHAROS:  P19793
GTEx:  ENSG00000186350 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19793
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.308 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.226 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 114.828α = 90
b = 100.271β = 90
c = 47.157γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
CNSrefinement
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-11-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-04-11
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Refinement description