2Q8S: X-Ray Crystal Structure Of The Nuclear Hormone Receptor Ppar-Gamma In A Complex With A Ppar GammaALPHA DUAL AGONIST

Citation:
Abstract
A new series of alpha-aryl or alpha-heteroarylphenyl propanoic acid derivatives was synthesized that incorporate acetylene-, ethylene-, propyl-, or nitrogen-derived linkers as a replacement of the commonly used ether moiety that joins the central phenyl ring with the lipophilic tail. The effect of these modifications in the binding and activation of PPARalpha and PPARgamma was first evaluated in vitro. Compounds possessing suitable profiles were then evaluated in the ob/ob mouse model of type 2 diabetes. The propylene derivative 40 and the propyl derivative 53 demonstrated robust plasma glucose lowering activity in this model. Compound 53 was also evaluated in male Zucker diabetic fatty rats and was found to achieve normalization of glucose, triglycerides, and insulin levels. An X-ray crystal structure of the complex of 53 with the PPARgamma-ligand-binding domain was obtained and discussed in this report.
PDB ID: 2Q8SDownload
MMDB ID: 67270
PDB Deposition Date: 2007/6/11
Updated in MMDB: 2008/10
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 2Q8S: dimeric; determined by author and by software (PISA)
Molecular Components in 2Q8S
Label Count Molecule
Proteins (2 molecules)
2
Peroxisome Proliferator-activated Receptor Gamma(Gene symbol: PPARG)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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