View source for 5wr0


==Huisgen cycloaddition for PPARg-LBD labeling by soaking method==
<StructureSection load='5wr0' size='340' side='right'caption='[[5wr0]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wr0]] 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=5WR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WR0 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]] 2.85&#8491;</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=5wr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wr0 OCA], [https://pdbe.org/5wr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wr0 RCSB], [https://www.ebi.ac.uk/pdbsum/5wr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wr0 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 ==
Site-specific labeling is an important methodology to elucidate the biological function of a target protein. Here, we report a strategy for site-specific chemical labeling, termed the "on-site reaction". We designed and readily synthesized a bifunctional ligand possessing two reaction sites, an enone and an azide moiety. This strategy involves an on-site conjugate addition reaction with protein followed by a Huisgen cycloaddition reaction. We demonstrate this strategy by using fluorescein as a probe and peroxisome proliferator activated receptor gamma (PPARgamma) as a target protein. The reactions were evaluated by ESI-mass analysis and the binding site and modes of binding were revealed by X-ray crystallization analysis. The proposed methodology can easily convert a covalent ligand into chemical tool for protein functional analysis and the identification of drug targets.

On-site reaction for PPARgamma modification using a specific bifunctional ligand.,Kojima H, Itoh T, Yamamoto K Bioorg Med Chem. 2017 Oct 23. pii: S0968-0896(17)31943-0. doi:, 10.1016/j.bmc.2017.10.024. PMID:29097031<ref>PMID:29097031</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5wr0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Itoh T]]
[[Category: Kojima H]]
[[Category: Yamamoto K]]