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PDBsum entry 2hwr

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protein ligands Protein-protein interface(s) links
Ligand binding protein PDB id
2hwr
Jmol
Contents
Protein chain
261 a.a. *
Ligands
DRD
Waters ×77
* Residue conservation analysis
PDB id:
2hwr
Name: Ligand binding protein
Title: Structural basis for the structure-activity relationships of peroxisome proliferator-activated receptor agonists
Structure: Peroxisome proliferator-activated receptor gamma. Chain: a, b. Fragment: ligand binding domain. Synonym: ppar-gamma. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.34Å     R-factor:   0.233     R-free:   0.316
Authors: Y.H.Peng,I.L.Lu,N.Mahindroo,C.H.Lin,H.P.Hsieh,S.Y.Wu
Key ref: N.Mahindroo et al. (2006). Structural basis for the structure-activity relationships of peroxisome proliferator-activated receptor agonists. J Med Chem, 49, 6421-6424. PubMed id: 17034149 DOI: 10.1021/jm060663c
Date:
01-Aug-06     Release date:   07-Aug-07    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma
Seq:
Struc:
505 a.a.
261 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: 10.1021/jm060663c J Med Chem 49:6421-6424 (2006)
PubMed id: 17034149  
 
 
Structural basis for the structure-activity relationships of peroxisome proliferator-activated receptor agonists.
N.Mahindroo, Y.H.Peng, C.H.Lin, U.K.Tan, E.Prakash, T.W.Lien, I.L.Lu, H.J.Lee, J.T.Hsu, X.Chen, C.C.Liao, P.C.Lyu, Y.S.Chao, S.Y.Wu, H.P.Hsieh.
 
  ABSTRACT  
 
Type 2 diabetes has rapidly reached an epidemic proportion becoming a major threat to global public health. PPAR agonists have emerged as a leading class of oral antidiabetic drugs. We report a structure biology analysis of novel indole-based PPAR agonists to explain the structure-activity relationships and present a critical analysis of reasons for change in selectivity with change in the orientation of the same scaffolds. The results would be helpful in designing novel PPAR agonists.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21482466 H.J.Gim, Y.J.Cheon, J.H.Ryu, and R.Jeon (2011).
Design and synthesis of benzoxazole containing indole analogs as peroxisome proliferator-activated receptor-γ/δ dual agonists.
  Bioorg Med Chem Lett, 21, 3057-3061.  
21157612 Y.Bhurruth-Alcor, T.Røst, M.R.Jorgensen, C.Kontogiorgis, J.Skorve, R.G.Cooper, J.M.Sheridan, W.D.Hamilton, J.R.Heal, R.K.Berge, and A.D.Miller (2011).
Synthesis of novel PPARα/γ dual agonists as potential drugs for the treatment of the metabolic syndrome and diabetes type II designed using a new de novo design program protobuild.
  Org Biomol Chem, 9, 1169-1188.  
19746174 S.N.Lewis, J.Bassaganya-Riera, and D.R.Bevan (2010).
Virtual Screening as a Technique for PPAR Modulator Discovery.
  PPAR Res, 2010, 861238.  
20734309 Y.H.Peng, M.S.Coumar, J.S.Leou, J.S.Wu, H.Y.Shiao, C.H.Lin, W.H.Lin, T.W.Lien, X.Chen, J.T.Hsu, Y.S.Chao, C.F.Huang, P.C.Lyu, H.P.Hsieh, and S.Y.Wu (2010).
Structural basis for the improved potency of peroxisome proliferator-activated receptor (PPAR) agonists.
  ChemMedChem, 5, 1707-1716.  
18398904 Y.C.Chou, E.Prakash, C.F.Huang, T.W.Lien, X.Chen, I.J.Su, Y.S.Chao, H.P.Hsieh, and J.T.Hsu (2008).
Bioassay-guided purification and identification of PPARalpha/gamma agonists from Chlorella sorokiniana.
  Phytother Res, 22, 605-613.  
17200111 L.Michalik, V.Zoete, G.Krey, A.Grosdidier, L.Gelman, P.Chodanowski, J.N.Feige, B.Desvergne, W.Wahli, and O.Michielin (2007).
Combined simulation and mutagenesis analyses reveal the involvement of key residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic behavior.
  J Biol Chem, 282, 9666-9677.  
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.