View source for 5lsg


==PPARgamma complex with the betulinic acid==
<StructureSection load='5lsg' size='340' side='right'caption='[[5lsg]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lsg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LSG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZQ:Betulinic+Acid'>QZQ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5lsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lsg OCA], [https://pdbe.org/5lsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lsg RCSB], [https://www.ebi.ac.uk/pdbsum/5lsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lsg ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Note=Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer.  Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9753710</ref>   Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:[https://omim.org/entry/604367 604367]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.<ref>PMID:12453919</ref> <ref>PMID:11788685</ref>   Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:[https://omim.org/entry/137800 137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.
== Function ==
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, and they serve as an alternative treatment for metabolic diseases. In this work, an affinity-based bioassay was found to be effective for selecting PPAR ligands from the dried extract of an African plant (Diospyros bipindensis). Among the ligands, we identified betulinic acid (BA), a compound already known for its anti-inflammatory, anti-tumour and antidiabetic properties, as a PPARgamma and PPARalpha antagonist. Cell differentiation assays showed that BA inhibits adipogenesis and promotes osteogenesis; either down-regulates or does not affect the expression of a series of adipogenic markers; and up-regulates the expression of osteogenic markers. Moreover, BA increases basal glucose uptake in 3T3-L1 adipocytes. The crystal structure of the complex of BA with PPARgamma sheds light, at the molecular level, on the mechanism by which BA antagonizes PPARgamma, and indicates a unique binding mode of this antagonist type. The results of this study show that the natural compound BA could be an interesting and safe candidate for the treatment of type 2 diabetes and bone diseases.

Betulinic acid is a PPARgamma antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis.,Brusotti G, Montanari R, Capelli D, Cattaneo G, Laghezza A, Tortorella P, Loiodice F, Peiretti F, Bonardo B, Paiardini A, Calleri E, Pochetti G Sci Rep. 2017 Jul 18;7(1):5777. doi: 10.1038/s41598-017-05666-6. PMID:28720829<ref>PMID:28720829</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lsg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Calleri E]]
[[Category: Capelli D]]
[[Category: Laghezza A]]
[[Category: Loiodice F]]
[[Category: Montanari R]]
[[Category: Paiardini A]]
[[Category: Pochetti G]]