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PDBsum entry 1y0s

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protein ligands metals Protein-protein interface(s) links
Hormone/growth factor receptor PDB id
1y0s
Jmol
Contents
Protein chains
260 a.a. *
Ligands
331 ×2
B7G ×2
Metals
IOD ×11
Waters ×162
* Residue conservation analysis
PDB id:
1y0s
Name: Hormone/growth factor receptor
Title: Crystal structure of ppar delta complexed with gw2331
Structure: Peroxisome proliferator activated receptor delta. Chain: a, b. Fragment: lbd domain (residues 170-441). Synonym: ppar-delta, ppar-beta, nuclear hormone receptor 1, nuc1, nuci. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.65Å     R-factor:   0.210     R-free:   0.261
Authors: I.Takada,R.T.Yu,H.E.Xu,R.X.Xu,M.H.Lambert,V.G.Montana, S.A.Kliewer,R.M.Evans,K.Umesono
Key ref: I.Takada et al. (2000). Alteration of a single amino acid in peroxisome proliferator-activated receptor-alpha (PPAR alpha) generates a PPAR delta phenotype. Mol Endocrinol, 14, 733-740. PubMed id: 10809235 DOI: 10.1210/mend.14.5.0456
Date:
16-Nov-04     Release date:   29-Mar-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q03181  (PPARD_HUMAN) -  Peroxisome proliferator-activated receptor delta
Seq:
Struc:
441 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: 10.1210/mend.14.5.0456 Mol Endocrinol 14:733-740 (2000)
PubMed id: 10809235  
 
 
Alteration of a single amino acid in peroxisome proliferator-activated receptor-alpha (PPAR alpha) generates a PPAR delta phenotype.
I.Takada, R.T.Yu, H.E.Xu, M.H.Lambert, V.G.Montana, S.A.Kliewer, R.M.Evans, K.Umesono.
 
  ABSTRACT  
 
Three pharmacologically important nuclear receptors, the peroxisome proliferator-activated receptors (PPARs alpha, gamma, and delta), mediate key transcriptional responses involved in lipid homeostasis. The PPAR alpha and gamma subtypes are well conserved from Xenopus to man, but the beta/delta subtypes display substantial species variations in both structure and ligand activation profiles. Characterization of the avian cognates revealed a close relationship between chick (c) alpha and gamma subtypes to their mammalian counterparts, whereas the third chicken subtype was intermediate to Xenopus (x) beta and mammalian delta, establishing that beta and delta are orthologs. Like xPPAR beta, cPPAR beta responded efficiently to hypolipidemic compounds that fail to activate the human counterpart. This provided the opportunity to address the pharmacological problem as to how drug selectivity is achieved and the more global evolutionary question as to the minimal changes needed to generate a new class of receptor. X-ray crystallography and chimeric analyses combined with site-directed mutagenesis of avian and mammalian cognates revealed that a Met to Val change at residue 417 was sufficient to switch the human and chick phenotype. These results establish that the genetic drive to evolve a novel and functionally selectable receptor can be modulated by a single amino acid change and suggest how nuclear receptors can accommodate natural variation in species physiology.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20706688 T.Coll, E.Barroso, D.Alvarez-Guardia, L.Serrano, L.Salvadó, M.Merlos, X.Palomer, and M.Vázquez-Carrera (2010).
The Role of Peroxisome Proliferator-Activated Receptor beta/delta on the Inflammatory Basis of Metabolic Disease.
  PPAR Res, 2010, 0.  
19622862 T.Oyama, K.Toyota, T.Waku, Y.Hirakawa, N.Nagasawa, J.I.Kasuga, Y.Hashimoto, H.Miyachi, and K.Morikawa (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.
PDB codes: 2znn 2zno 2znp 2znq
18558802 K.Kato, Y.Oka, and M.K.Park (2008).
Identification and expression analysis of peroxisome proliferator-activated receptors cDNA in a reptile, the leopard gecko (Eublepharis macularius).
  Zoolog Sci, 25, 492-502.  
18092840 P.Sertznig, M.Seifert, W.Tilgen, and J.Reichrath (2008).
Peroxisome proliferator-activated receptors (PPARs) and the human skin: importance of PPARs in skin physiology and dermatologic diseases.
  Am J Clin Dermatol, 9, 15-31.  
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.  
17443682 P.Sertznig, M.Seifert, W.Tilgen, and J.Reichrath (2007).
Present concepts and future outlook: function of peroxisome proliferator-activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer.
  J Cell Physiol, 212, 1.  
16511591 G.D.Barish, V.A.Narkar, and R.M.Evans (2006).
PPAR delta: a dagger in the heart of the metabolic syndrome.
  J Clin Invest, 116, 590-597.  
14993764 H.Uchiki, and H.Miyachi (2004).
Molecular modeling study of species-selective peroxisome proliferator-activated receptor (PPAR) alpha agonist; possible mechanism(s) of human PPARalpha selectivity of an alpha-substituted phenylpropanoic acid derivative (KCL).
  Chem Pharm Bull (Tokyo), 52, 365-367.  
14646253 H.Kojo, M.Fukagawa, K.Tajima, A.Suzuki, T.Fujimura, I.Aramori, K.Hayashi, and S.Nishimura (2003).
Evaluation of human peroxisome proliferator-activated receptor (PPAR) subtype selectivity of a variety of anti-inflammatory drugs based on a novel assay for PPAR delta(beta).
  J Pharmacol Sci, 93, 347-355.  
14530391 Y.Kamei, H.Ohizumi, Y.Fujitani, T.Nemoto, T.Tanaka, N.Takahashi, T.Kawada, M.Miyoshi, O.Ezaki, and A.Kakizuka (2003).
PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity.
  Proc Natl Acad Sci U S A, 100, 12378-12383.  
11698662 H.E.Xu, M.H.Lambert, V.G.Montana, K.D.Plunket, L.B.Moore, J.L.Collins, J.A.Oplinger, S.A.Kliewer, R.T.Gampe, D.D.McKee, J.T.Moore, and T.M.Willson (2001).
Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors.
  Proc Natl Acad Sci U S A, 98, 13919-13924.
PDB codes: 1k74 1k7l
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 codes are shown on the right.