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PDBsum entry 3gd2

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protein ligands Protein-protein interface(s) links
Transcription/transcrition activator PDB id
3gd2
Jmol
Contents
Protein chains
227 a.a. *
11 a.a. *
Ligands
708
Waters ×25
* Residue conservation analysis
PDB id:
3gd2
Name: Transcription/transcrition activator
Title: Isoxazole ligand bound to farnesoid x receptor (fxr)
Structure: Bile acid receptor. Chain: a. Fragment: farsenoid x receptor. Synonym: farnesoid x-activated receptor, farnesol receptor hrr-1, nuclear receptor subfamily 1 group h member 4, retinoid x receptor-interacting protein 14, rxr-interacting protein 14. Engineered: yes. Mutation: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nr1h4, bar, fxr, hrr1, rip14. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes
Resolution:
3.20Å     R-factor:   0.242     R-free:   0.297
Authors: K.P.Madauss,S.P.Williams,D.N.Deaton,G.B.Wisely,R.B.Mcfadyen
Key ref: J.Y.Bass et al. (2009). Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064. Bioorg Med Chem Lett, 19, 2969-2973. PubMed id: 19410460 DOI: 10.1016/j.bmcl.2009.04.047
Date:
23-Feb-09     Release date:   07-Jul-09    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q96RI1  (NR1H4_HUMAN) -  Bile acid receptor
Seq:
Struc:
486 a.a.
227 a.a.*
Protein chain
No UniProt id for this chain
Struc: 11 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  

 

 
DOI no: 10.1016/j.bmcl.2009.04.047 Bioorg Med Chem Lett 19:2969-2973 (2009)
PubMed id: 19410460  
 
 
Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064.
J.Y.Bass, R.D.Caldwell, J.A.Caravella, L.Chen, K.L.Creech, D.N.Deaton, K.P.Madauss, H.B.Marr, R.B.McFadyen, A.B.Miller, D.J.Parks, D.Todd, S.P.Williams, G.B.Wisely.
 
  ABSTRACT  
 
Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19963001 D.L.Howarth, S.H.Law, J.M.Law, J.A.Mondon, S.W.Kullman, and D.E.Hinton (2010).
Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes).
  Toxicol Appl Pharmacol, 243, 111-121.  
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