6jf0
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Covalent labeling of hPPARg-LBD by turn-on fluorescent probe mediated by conjugate addition and cyclization== | |
| + | <StructureSection load='6jf0' size='340' side='right'caption='[[6jf0]], [[Resolution|resolution]] 3.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6jf0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JF0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EB6:methyl+(2~{S})-3-[4-[3-(4-methoxy-2-oxidanyl-phenyl)prop-2-ynoyloxy]phenyl]-2-[[2-(phenylcarbonyl)phenyl]amino]propanoate'>EB6</scene>, <scene name='pdbligand=EBF:7-methoxychromen-2-one'>EBF</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jf0 OCA], [http://pdbe.org/6jf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jf0 RCSB], [http://www.ebi.ac.uk/pdbsum/6jf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jf0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://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:[http://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:[http://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:[http://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 == | ||
| + | [[http://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 == | ||
| + | Fluorescent molecules have contributed to basic biological research but there are currently only a limited number of probes available for the detection of non-enzymatic proteins. Here, we report turn-on fluorescent probes mediated by conjugate addition and cyclization (TCC probes). These probes react with multiple amino acids and exhibit a 36-fold greater emission intensity after reaction. We analyzed the reactions between TCC probes and nuclear receptors by electrospray ionization mass spectrometry, X-ray crystallography, spectrofluorometry, and fluorescence microscopy. In vitro analysis showed that probes consisting of a protein ligand and TCC could label vitamin D receptor and peroxisome proliferator-activated receptor gamma. Moreover, we demonstrated that not only a ligand unit but also a peptide unit can label the target protein in a complex mixture. | ||
| - | + | Cyclization Reaction-Based Turn-on Probe for Covalent Labeling of Target Proteins.,Kojima H, Fujita Y, Takeuchi R, Ikebe Y, Ohashi N, Yamamoto K, Itoh T Cell Chem Biol. 2020 Jan 22. pii: S2451-9456(20)30006-4. doi:, 10.1016/j.chembiol.2020.01.006. PMID:31991094<ref>PMID:31991094</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6jf0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Itoh, T]] | [[Category: Itoh, T]] | ||
| - | [[Category: Yamamoto, K]] | ||
[[Category: Kojima, H]] | [[Category: Kojima, H]] | ||
| + | [[Category: Yamamoto, K]] | ||
| + | [[Category: Covalent labeling]] | ||
| + | [[Category: Cysteine]] | ||
| + | [[Category: Nuclear protein]] | ||
| + | [[Category: Receptor]] | ||
| + | [[Category: Tcc probe]] | ||
| + | [[Category: Turn-on fluorescent probe]] | ||
Revision as of 04:08, 13 February 2020
Covalent labeling of hPPARg-LBD by turn-on fluorescent probe mediated by conjugate addition and cyclization
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