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PDBsum entry 1nyx

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protein ligands Protein-protein interface(s) links
Transcription PDB id
1nyx
Jmol
Contents
Protein chain
260 a.a. *
Ligands
DRF
Waters ×85
* Residue conservation analysis
PDB id:
1nyx
Name: Transcription
Title: Ligand binding domain of the human peroxisome proliferator activated receptor gamma in complex with an agonist
Structure: Peroxisome proliferator activated receptor gamma. Chain: a, b. Fragment: ligand binding domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.65Å     R-factor:   0.240     R-free:   0.306
Authors: S.Ebdrup,I.Pettersson,H.B.Rasmussen,H.-J.Deussen,A.Frost Jensen,S.B.Mortensen,J.Fleckner,L.Pridal,L.Nygaard, P.Sauerberg
Key ref: S.Ebdrup et al. (2003). Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar. J Med Chem, 46, 1306-1317. PubMed id: 12672231 DOI: 10.1021/jm021027r
Date:
14-Feb-03     Release date:   15-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma
Seq:
Struc:
505 a.a.
260 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/jm021027r J Med Chem 46:1306-1317 (2003)
PubMed id: 12672231  
 
 
Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar.
S.Ebdrup, I.Pettersson, H.B.Rasmussen, H.J.Deussen, A.Frost Jensen, S.B.Mortensen, J.Fleckner, L.Pridal, L.Nygaard, P.Sauerberg.
 
  ABSTRACT  
 
A new and improved synthesis of the peroxisome proliferator-activated receptor (PPAR) agonist ragaglitazar applicable for large-scale preparation has been developed. The convergent synthetic procedure was based on a novel enzymatic kinetic resolution step. The conformation of ragaglitazar bound to the hPPARgamma receptor was quite different compared to the single-crystal structures of the l-arginine salt of ragaglitazar. In particular, the phenoxazine ring system had varying orientations. Ragaglitazar had high affinity for the hPPARalpha and -gamma receptors with IC(50) values of 0.98 and 0.092 microM, respectively. The lack of hPPARdelta activity could be explained by the absence of binding in the tail-up pocket in the hPPARdelta receptor, in contrast to the hPPARdelta agonist GW2433, which was able to bind in both the tail-up and tail-down pockets of the receptor.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20496064 J.Fidelak, S.Ferrer, M.Oberlin, D.Moras, A.Dejaegere, and R.H.Stote (2010).
Dynamic correlation networks in human peroxisome proliferator-activated receptor-γ nuclear receptor protein.
  Eur Biophys J, 39, 1503-1512.  
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.  
19067454 Y.Tanrikulu, O.Rau, O.Schwarz, E.Proschak, K.Siems, L.Müller-Kuhrt, M.Schubert-Zsilavecz, and G.Schneider (2009).
Structure-based pharmacophore screening for natural-product-derived PPARgamma agonists.
  Chembiochem, 10, 75-78.  
19197366 M.B.Oleksiewicz, J.Southgate, L.Iversen, and F.L.Egerod (2008).
Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARalpha + gamma Agonists.
  PPAR Res, 2008, 103167.  
17963209 O.Rau, H.Zettl, L.Popescu, D.Steinhilber, and M.Schubert-Zsilavecz (2008).
The treatment of dyslipidemia--what's left in the pipeline?
  ChemMedChem, 3, 206-221.  
18718125 W.Ji, L.Guo, J.Lian, and B.Gong (2008).
Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats.
  J Pharm Pharmacol, 60, 1207-1212.  
17462987 A.L.Ambrosio, S.M.Dias, I.Polikarpov, R.B.Zurier, S.H.Burstein, and R.C.Garratt (2007).
Ajulemic acid, a synthetic nonpsychoactive cannabinoid acid, bound to the ligand binding domain of the human peroxisome proliferator-activated receptor gamma.
  J Biol Chem, 282, 18625-18633.
PDB code: 2om9
17357171 G.Fracchiolla, A.Laghezza, L.Piemontese, G.Carbonara, A.Lavecchia, P.Tortorella, M.Crestani, E.Novellino, and F.Loiodice (2007).
Synthesis, Biological Evaluation, and Molecular Modeling Investigation of Chiral Phenoxyacetic Acid Analogues with PPARalpha and PPARgamma Agonist Activity.
  ChemMedChem, 2, 641-654.  
17403688 G.Pochetti, C.Godio, N.Mitro, D.Caruso, A.Galmozzi, S.Scurati, F.Loiodice, G.Fracchiolla, P.Tortorella, A.Laghezza, A.Lavecchia, E.Novellino, F.Mazza, and M.Crestani (2007).
Insights into the mechanism of partial agonism: crystal structures of the peroxisome proliferator-activated receptor gamma ligand-binding domain in the complex with two enantiomeric ligands.
  J Biol Chem, 282, 17314-17324.
PDB codes: 2i4j 2i4p 2i4z
17441160 H.Kakei, R.Tsuji, T.Ohshima, H.Morimoto, S.Matsunaga, and M.Shibasaki (2007).
Catalytic asymmetric epoxidation of alpha,beta-unsaturated esters with chiral yttrium-biaryldiol complexes.
  Chem Asian J, 2, 257-264.  
17937915 J.B.Bruning, M.J.Chalmers, S.Prasad, S.A.Busby, T.M.Kamenecka, Y.He, K.W.Nettles, and P.R.Griffin (2007).
Partial agonists activate PPARgamma using a helix 12 independent mechanism.
  Structure, 15, 1258-1271.
PDB codes: 2q59 2q5p 2q5s 2q61 2q6r 2q6s
17960326 P.Markt, D.Schuster, J.Kirchmair, C.Laggner, and T.Langer (2007).
Pharmacophore modeling and parallel screening for PPAR ligands.
  J Comput Aided Mol Des, 21, 575-590.  
16626515 Z.F.Cai, Q.Liu, P.P.Li, Z.R.Guo, and Z.F.Shen (2006).
Synthesis and anti-diabetic activity of (RS)-2-ethoxy-3-{4-[2-(4-trifluoro-methanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid.
  Acta Pharmacol Sin, 27, 597-602.  
16240504 F.L.Egerod, H.S.Nielsen, L.Iversen, I.Thorup, T.Storgaard, and M.B.Oleksiewicz (2005).
Biomarkers for early effects of carcinogenic dual-acting PPAR agonists in rat urinary bladder urothelium in vivo.
  Biomarkers, 10, 295-309.  
16076770 M.B.Oleksiewicz, I.Thorup, H.S.Nielsen, H.V.Andersen, A.C.Hegelund, L.Iversen, T.S.Guldberg, P.R.Brinck, I.Sjogren, U.K.Thinggaard, L.Jørgensen, and M.B.Jensen (2005).
Generalized cellular hypertrophy is induced by a dual-acting PPAR agonist in rat urinary bladder urothelium in vivo.
  Toxicol Pathol, 33, 552-560.  
15271292 A.L.Parrill, V.M.Sardar, and H.Yuan (2004).
Sphingosine 1-phosphate and lysophosphatidic acid receptors: agonist and antagonist binding and progress toward development of receptor-specific ligands.
  Semin Cell Dev Biol, 15, 467-476.  
14642685 J.Plutzky (2003).
Peroxisome proliferator-activated receptors as therapeutic targets in inflammation.
  J Am Coll Cardiol, 42, 1764-1766.  
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.