7wox
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==PPARgamma antagonist (MMT-160)- PPARgamma LBD complex== | |
| + | <StructureSection load='7wox' size='340' side='right'caption='[[7wox]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WOX 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]] 3.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5YW:N-[[5-(3-phenylprop-2-ynoylamino)-2-propoxy-phenyl]methyl]-4-pyrimidin-2-yl-benzamide'>5YW</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=7wox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wox OCA], [https://pdbe.org/7wox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wox RCSB], [https://www.ebi.ac.uk/pdbsum/7wox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wox ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Peroxisome proliferator-activated receptor gamma (PPARgamma) antagonists are drug candidates for the treatment of type 2 diabetes, obesity, and osteoporosis. Previously, we have designed and synthesized a series of substituted phenylalkynyl amide-type PPARgamma antagonists. The representative compound, MMT-160, exhibited nanomolar-order PPARgamma antagonistic activity. To understand the antagonistic mode of action of MMT-160, mass spectrometric and X-ray crystallographic analysis of MMT-160 in the presence of the PPARgamma ligand binding domain (LBD) were performed. The mass spectrometry results clearly indicated that alkynyl amide-type PPARgamma antagonists were covalently bound to the PPARgamma LBD. The X-ray crystallographic analysis indicated that MMT-160 acted as a Michael acceptor and covalently bound to the PPARgamma LBD via Cys285. In addition, MMT-160 bound to the PPARgamma LBD with a binding mode that was different from the binding modes observed for PPARgamma agonists and partial agonists. | ||
| - | + | Arylalkynyl amide-type peroxisome proliferator-activated receptor gamma (PPARgamma)-selective antagonists covalently bind to the PPARgamma ligand binding domain with a unique binding mode.,Yoshizawa M, Aoyama T, Itoh T, Miyachi H Bioorg Med Chem Lett. 2022 May 15;64:128676. doi: 10.1016/j.bmcl.2022.128676., Epub 2022 Mar 15. PMID:35301139<ref>PMID:35301139</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7wox" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Aoyama T]] | ||
| + | [[Category: Itoh T]] | ||
| + | [[Category: Miyachi H]] | ||
| + | [[Category: Yoshizawa M]] | ||
Current revision
PPARgamma antagonist (MMT-160)- PPARgamma LBD complex
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