6ZLY
Crystal structure of the complex between PPARgamma LBD and the ligand NV1362 (7a)
Summary for 6ZLY
| Entry DOI | 10.2210/pdb6zly/pdb |
| Descriptor | Peroxisome proliferator-activated receptor gamma, (2~{S})-2-[(4-hexoxyphenyl)carbonylamino]-3-methyl-butanoic acid (3 entities in total) |
| Functional Keywords | transcription factor, transcription |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 68762.42 |
| Authors | Pochetti, G.,Montanari, R.,Capelli, D. (deposition date: 2020-07-01, release date: 2020-11-25, Last modification date: 2024-01-31) |
| Primary citation | Peiretti, F.,Montanari, R.,Capelli, D.,Bonardo, B.,Colson, C.,Amri, E.Z.,Grimaldi, M.,Balaguer, P.,Ito, K.,Roeder, R.G.,Pochetti, G.,Brunel, J.M. A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor gamma Binding Properties and Biological Activities. J.Med.Chem., 63:13124-13139, 2020 Cited by PubMed Abstract: A proprietary library of novel -aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound that possesses weak proadipogenic and peroxisome proliferator-activated receptor γ (PPARγ) activating properties. The systematic optimization of , in order to improve its PPARγ agonist activity, led to the synthesis of compound (-aryl-substituted valine derivative) that possesses dual PPARγ/PPARα agonistic activity. Structural and kinetic analyses reveal that occupies the typical ligand binding domain of the PPARγ agonists with, however, a unique high-affinity binding mode. Furthermore, is highly effective in preventing cyclin-dependent kinase 5-mediated phosphorylation of PPARγ serine 273. Although less proadipogenic than rosiglitazone, significantly increases adipocyte insulin-stimulated glucose uptake and efficiently promotes white-to-brown adipocyte conversion. In addition, prevents oleic acid-induced lipid accumulation in hepatoma cells. The unique biochemical properties and biological activities of compound suggest that it would be a promising candidate for the development of compounds to reduce insulin resistance, obesity, and nonalcoholic fatty liver disease. PubMed: 33142057DOI: 10.1021/acs.jmedchem.0c01555 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.79 Å) |
Structure validation
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