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PDBsum entry 4dqm

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protein ligands Protein-protein interface(s) links
Transcription/transferase PDB id
4dqm
Jmol
Contents
Protein chains
234 a.a.
Ligands
LYS-SER-LEU-LEU-
GLN-GLN-LEU-LEU-
THR-GLU
×2
LUF ×2
Waters ×31
PDB id:
4dqm
Name: Transcription/transferase
Title: Revealing a marine natural product as a novel agonist for re acid receptors with a unique binding mode and antitumor act
Structure: Retinoic acid receptor alpha. Chain: a, c. Fragment: ligand binding domain, unp residues 182-415. Synonym: rar-alpha, nuclear receptor subfamily 1 group b me engineered: yes. Nuclear receptor coactivator 1. Chain: b, d. Fragment: lxxll motif 7, unp residues 1432-1441. Synonym: ncoa-1, class e basic helix-loop-helix protein 74,
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nr1b1, rara. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized.
Resolution:
2.75Å     R-factor:   0.216     R-free:   0.259
Authors: S.Wang,Z.Wang,S.Lin,W.Zheng,R.Wang,S.Jin,J.Chen,L.Jin,Y.Li
Key ref: S.Wang et al. (2012). Revealing a natural marine product as a novel agonist for retinoic acid receptors with a unique binding mode and inhibitory effects on cancer cells. Biochem J, 446, 79-87. PubMed id: 22642567 DOI: 10.1042/BJ20120726
Date:
16-Feb-12     Release date:   03-Oct-12    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P10276  (RARA_HUMAN) -  Retinoic acid receptor alpha
Seq:
Struc:
462 a.a.
234 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   3 terms 
  Biochemical function     DNA binding     4 terms  

 

 
DOI no: 10.1042/BJ20120726 Biochem J 446:79-87 (2012)
PubMed id: 22642567  
 
 
Revealing a natural marine product as a novel agonist for retinoic acid receptors with a unique binding mode and inhibitory effects on cancer cells.
S.Wang, Z.Wang, S.Lin, W.Zheng, R.Wang, S.Jin, J.Chen, L.Jin, Y.Li.
 
  ABSTRACT  
 
Retinoids display anti-tumour activity on various cancer cells and therefore have been used as important therapeutic agents. However, adverse side effects and RA (retinoic acid) resistance limit further development and clinical application of retinoid-based therapeutic agents. We report in the present paper the identification of a natural marine product that activates RARs (RA receptors) with a chemical structure distinct from retinoids by high-throughput compound library screening. Luffariellolide was uncovered as a novel RAR agonist by inducing co-activator binding to these receptors in vitro, further inhibiting cell growth and regulating RAR target genes in various cancer cells. Structural and molecular studies unravelled a unique binding mode of this natural ligand to RARs with an unexpected covalent modification on the RAR. Functional characterization further revealed that luffariellolide displays chemotherapeutic potentials for overcoming RA resistance in colon cancer cells, suggesting that luffariellolide may represent a unique template for designing novel non-retinoid compounds with advantages over current RA drugs.