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PDBsum entry 2ewp

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protein ligands Protein-protein interface(s) links
Transcription PDB id
2ewp
Jmol
Contents
Protein chains
224 a.a. *
Ligands
TXF ×5
Waters ×412
* Residue conservation analysis
PDB id:
2ewp
Name: Transcription
Title: Crystal structure of estrogen related receptor-3 (err-gamma) binding domaind with tamoxifen analog gsk5182
Structure: Estrogen-related receptor gamma. Chain: a, b, c, d, e. Synonym: estrogen receptor-related protein 3, err gamma-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: esrrg, err3, errg2, kiaa0832, nr3b3. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
2.30Å     R-factor:   0.188     R-free:   0.247
Authors: R.T.Nolte
Key ref: E.Y.Chao et al. (2006). Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma. Bioorg Med Chem Lett, 16, 821-824. PubMed id: 16307879 DOI: 10.1016/j.bmcl.2005.11.030
Date:
04-Nov-05     Release date:   09-May-06    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P62508  (ERR3_HUMAN) -  Estrogen-related receptor gamma
Seq:
Struc:
458 a.a.
224 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   2 terms 
  Biochemical function     DNA binding     4 terms  

 

 
DOI no: 10.1016/j.bmcl.2005.11.030 Bioorg Med Chem Lett 16:821-824 (2006)
PubMed id: 16307879  
 
 
Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma.
E.Y.Chao, J.L.Collins, S.Gaillard, A.B.Miller, L.Wang, L.A.Orband-Miller, R.T.Nolte, D.P.McDonnell, T.M.Willson, W.J.Zuercher.
 
  ABSTRACT  
 
The design and synthesis of 4-hydroxytamoxifen (4-OHT) derivatives are described. The binding affinities of these compounds toward the orphan estrogen-related receptor gamma and the classical estrogen receptor alpha demonstrate that analogs bearing hydroxyalkyl groups display improved binding selectivity profiles compared with that of 4-OHT. An X-ray crystal structure of one of the designed compounds bound to ERRgamma LBD confirms the molecular basis of the selectivity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
23192231 G.Deblois, and V.Giguère (2013).
Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond.
  Nat Rev Cancer, 13, 27-36.  
21284981 J.M.Tennessen, K.D.Baker, G.Lam, J.Evans, and C.S.Thummel (2011).
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
  Cell Metab, 13, 139-148.  
20135221 M.Koh, and S.B.Park (2011).
Computer-aided design and synthesis of tetra-aryl-substituted alkenes and their bioevaluation as a selective modulator of estrogen-related receptor γ.
  Mol Divers, 15, 69-81.  
19090659 G.Bottegoni, I.Kufareva, M.Totrov, and R.Abagyan (2009).
Four-dimensional docking: a fast and accurate account of discrete receptor flexibility in ligand docking.
  J Med Chem, 52, 397-406.  
19690166 Y.B.Xie, J.H.Park, D.K.Kim, J.H.Hwang, S.Oh, S.B.Park, M.Shong, I.K.Lee, and H.S.Choi (2009).
Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation.
  J Biol Chem, 284, 28762-28774.  
18174917 A.M.Tremblay, and V.Giguère (2007).
The NR3B subgroup: an ovERRview.
  Nucl Recept Signal, 5, e009.  
17488637 C.R.Dufour, B.J.Wilson, J.M.Huss, D.P.Kelly, W.A.Alaynick, M.Downes, R.M.Evans, M.Blanchette, and V.Giguère (2007).
Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma.
  Cell Metab, 5, 345-356.  
17556356 J.Kallen, R.Lattmann, R.Beerli, A.Blechschmidt, M.J.Blommers, M.Geiser, J.Ottl, J.M.Schlaeppi, A.Strauss, and B.Fournier (2007).
Crystal structure of human estrogen-related receptor alpha in complex with a synthetic inverse agonist reveals its novel molecular mechanism.
  J Biol Chem, 282, 23231-23239.
PDB code: 2pjl
16914190 P.Ascenzi, A.Bocedi, and M.Marino (2006).
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
  Mol Aspects Med, 27, 299-402.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.