7wox | pdb_00007wox

PPARgamma antagonist (MMT-160)- PPARgamma LBD complex

spinqualitylabelsall models 7wox, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: 5YW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Peroxisome proliferator-activated receptor 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA