PDBsum entry 2znn

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Transcription PDB id
Protein chain
258 a.a. *
Waters ×146
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Human pprr alpha ligand binding domain in complex with a syn agonist tipp703
Structure: Peroxisome proliferator-activated receptor alpha. Chain: a. Fragment: ligand binding domain. Synonym: ppar-alpha, nuclear receptor subfamily 1 group c m engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ppara, nr1c1, ppar. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
2.01Å     R-factor:   0.214     R-free:   0.253
Authors: T.Oyama,K.Toyota,J.Kasuga,H.Miyachi,K.Morikawa
Key ref:
T.Oyama et al. (2009). Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures. Acta Crystallogr D Biol Crystallogr, 65, 786-795. PubMed id: 19622862 DOI: 10.1107/S0907444909015935
30-Apr-08     Release date:   05-May-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q07869  (PPARA_HUMAN) -  Peroxisome proliferator-activated receptor alpha
468 a.a.
258 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: 10.1107/S0907444909015935 Acta Crystallogr D Biol Crystallogr 65:786-795 (2009)
PubMed id: 19622862  
Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures.
T.Oyama, K.Toyota, T.Waku, Y.Hirakawa, N.Nagasawa, J.I.Kasuga, Y.Hashimoto, H.Miyachi, K.Morikawa.
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPARalpha and PPARgamma LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD-ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPARdelta LBD in complex with an alpha/delta-selective ligand, TIPP-401, and with a related delta-specific ligand, TIPP-204, were also determined. The comparison between the two PPARdelta complexes revealed how each ligand exhibits either a ;dual selective' or ;single specific' binding mode.
  Selected figure(s)  
Figure 2.
Figure 2 Close-up views of the ligand-binding pockets. (a) PPAR LBD-TIPP-703. (b) PPAR LBD-TIPP-703. (c) PPAR LBD-TIPP-401. (d) PPAR LBD-TIPP-204. The left column shows the OMIT F[o] - F[c] electron-density maps (contoured at 2.2 ) and the right columns show stereoviews of the interaction between the ligand-binding pockets and the bound ligands. The amino-acid residues contacting the ligands are labelled.
Figure 4.
Figure 4 Comparison between the PPAR LBD-TIPP-703 and the PPAR LBD-TIPP-204 complexes. (a) Stereoview of the superimposed structures. The PPAR LBD-TIPP-703 complex is coloured cyan and the PPAR LBD-TIPP-204 complex is coloured magenta. The key contact residues of the complexes are highlighted. Prominent interactions in each complex are indicated by arrows. (b) Schematic view of the protein-ligand interactions, highlighting the specificity of TIPP-204 toward PPAR .
  The above figures are reprinted from an Open Access publication published by the IUCr: Acta Crystallogr D Biol Crystallogr (2009, 65, 786-795) copyright 2009.  
  Figures were selected by an automated process.