3OZJ

Crystal structure of human retinoic X receptor alpha complexed with bigelovin and coactivator SRC-1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Work: 0.245 
  • R-Value Observed: 0.245 

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Literature

Structure basis of bigelovin as a selective RXR agonist with a distinct binding mode

Zhang, H.Li, L.Chen, L.Hu, L.Jiang, H.Shen, X.

(2011) J Mol Biol 407: 13-20

  • DOI: https://doi.org/10.1016/j.jmb.2011.01.032
  • Primary Citation of Related Structures:  
    3OZJ

  • PubMed Abstract: 

    The nuclear receptor retinoid X receptor (RXR) functions potently in the regulation of homeostasis and cell development, while rexinoids as RXR agonists have proved their therapeutic potential in the treatment of metabolic diseases and cancer. Here, the natural product bigelovin was identified as a selective RXRα agonist. Interestingly, this compound could not transactivate RXRα:RXRα homodimer but could enhance the transactivation of RXRα:peroxisome proliferator-activated receptor γ heterodimer and repress that of RXRα:liver X receptor (LXR) α heterodimer, while it had no effects on RXRα:farnesoid X receptor heterodimer. Considering that the effective role of LXR response element involved transactivation of sterol regulatory element-binding protein-1c mediated by RXRα:LXRα in triglyceride elevation, such LXR response element repressing by bigelovin has obviously addressed its potency for further research. Moreover, our determined crystal structure of the bigelovin-activated RXRα ligand-binding domain with the coactivator human steroid receptor coactivator-1 peptide revealed that bigelovin adopted a distinct binding mode. Compared with the known RXR ligands, bigelovin lacks the acidic moiety in structure, which indicated that the acidic moiety rendered little effects on RXR activation. Our results have thereby provided new insights into the structure-based selective rexinoids design with bigelovin as a potential lead compound.


  • Organizational Affiliation

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


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Retinoic acid receptor RXR-alpha
A, C
238Homo sapiensMutation(s): 0 
Gene Names: RXRANR2B1
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
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
SRC-1, peptide of Nuclear receptor coactivator 2
B, D
11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15596 (Homo sapiens)
Explore Q15596 
Go to UniProtKB:  Q15596
PHAROS:  Q15596
GTEx:  ENSG00000140396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15596
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BGV
Query on BGV

Download Ideal Coordinates CCD File 
E [auth A],
F [auth C]
(3aR,4S,4aR,7aR,8R,9aS)-4a,8-dimethyl-3-methylidene-2,5-dioxo-2,3,3a,4,4a,5,7a,8,9,9a-decahydroazuleno[6,5-b]furan-4-yl acetate
C17 H20 O5
DCNRYQODUSSOKC-MMLVVLEOSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
BGV PDBBind:  3OZJ Kd: 7700 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Work: 0.245 
  • R-Value Observed: 0.245 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.4α = 90
b = 66.59β = 90
c = 111.73γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-04-18
    Changes: Database references
  • Version 1.3: 2022-08-24
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-11-01
    Changes: Data collection, Refinement description