4RE8

Crystal Structure of TR3 LBD in complex with Molecule 5


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity

Wang, W.J.Wang, Y.Hou, P.P.Li, F.W.Zhou, B.Chen, H.Z.Bian, X.L.Cai, Q.X.Xing, Y.Z.He, J.P.Zhang, H.Huang, P.Q.Lin, T.Wu, Q.

(2015) Chem Biol 22: 1040-1051

  • DOI: https://doi.org/10.1016/j.chembiol.2015.06.023
  • Primary Citation of Related Structures:  
    4RE8, 4REE, 4REF, 4WHF, 4WHG

  • PubMed Abstract: 

    Apoptotic resistance is becoming a significant obstacle for cancer therapy as the majority of treatment takes the route of apoptotic induction. It is of great importance to develop an alternative strategy to induce cancer cell death. We previously reported that autophagic cell death mediated by nuclear receptor TR3 and driven by a chemical agonist, 1-(3,4,5-trihydroxyphenyl)nonan-1-one (THPN), is highly effective in the therapy of melanoma but not any other cancer types. Here, we discovered that the insensitivity of cancer cells to THPN originated from a high cellular Akt2 activity. Akt2 phosphorylation interferes with TR3 export to cytoplasm and targeting to mitochondria, which lead to the autophagic induction. Therefore, the TR3-mediated autophagy could be effectively induced in the otherwise insensitive cells by downregulating Akt2 activity. Highly effective antineoplastic compounds are developed through optimizing the structure of THPN. This study implicates a general strategy for cancer therapy by the induction of autophagic cell death.


  • Organizational Affiliation

    State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian Province, P.R. China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor subfamily 4 group A member 1A [auth B],
B [auth A]
256Homo sapiensMutation(s): 0 
Gene Names: GFRP1HMRNAK1NR4A1
UniProt & NIH Common Fund Data Resources
Find proteins for P22736 (Homo sapiens)
Explore P22736 
Go to UniProtKB:  P22736
PHAROS:  P22736
GTEx:  ENSG00000123358 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22736
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.635α = 90
b = 76.524β = 90
c = 128.627γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-09
    Type: Initial release
  • Version 1.1: 2017-11-22
    Changes: Refinement description
  • Version 1.2: 2024-03-20
    Changes: Data collection, Database references, Derived calculations, Refinement description