8ADF
X-ray crystal structure of PPAR gamma ligand binding domain in complex with CZ39
Summary for 8ADF
| Entry DOI | 10.2210/pdb8adf/pdb |
| Descriptor | Peroxisome proliferator-activated receptor gamma, (2R)-3-(4-bromophenyl)-2-(3-hydroxyphenyl)-4-oxidanyl-2H-furan-5-one (3 entities in total) |
| Functional Keywords | nuclear receptor, transcription |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 69533.79 |
| Authors | Capelli, D.,Montanari, R.,Pochetti, G.,Meneghetti, F.,Villa, S. (deposition date: 2022-07-08, release date: 2023-04-26, Last modification date: 2024-02-07) |
| Primary citation | Capelli, D.,Cazzaniga, G.,Mori, M.,Laghezza, A.,Loiodice, F.,Quaglia, M.,Negro, E.,Meneghetti, F.,Villa, S.,Montanari, R. Biological Screening and Crystallographic Studies of Hydroxy gamma-Lactone Derivatives to Investigate PPAR gamma Phosphorylation Inhibition. Biomolecules, 13:-, 2023 Cited by PubMed Abstract: PPARγ represents a key target for the treatment of type 2 diabetes and metabolic syndrome. To avoid serious adverse effects related to the PPARγ agonism profile of traditional antidiabetic drugs, a new opportunity is represented by the development of molecules acting as inhibitors of PPARγ phosphorylation by the cyclin-dependent kinase 5 (CDK5). Their mechanism of action is mediated by the stabilization of the PPARγ β-sheet containing Ser273 (Ser245 in PPARγ isoform 1 nomenclature). In this paper, we report the identification of new γ-hydroxy-lactone-based PPARγ binders from the screening of an in-house library. These compounds exhibit a non-agonist profile towards PPARγ, and one of them prevents Ser245 PPARγ phosphorylation by acting mainly on PPARγ stabilization and exerting a weak CDK5 inhibitory effect. PubMed: 37189440DOI: 10.3390/biom13040694 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.13 Å) |
Structure validation
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