8C0C

X-ray crystal structure of PPAR gamma ligand binding domain in complex with CZ46

8C0C の概要

• エントリーDOI: 10.2210/pdb8c0c/pdb
• 分子名称: Peroxisome proliferator-activated receptor gamma, (2~{R})-2-[4-(naphthalen-1-ylmethoxy)phenyl]-4-oxidanyl-3-phenyl-2~{H}-furan-5-one (3 entities in total)
• 機能のキーワード: ppar, nuclear receptor, transcription, nuclear protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69247.91

構造登録者

Capelli, D.,Montanari, R.,Pochetti, G.,Villa, S.,Meneghetti, F. (登録日: 2022-12-16, 公開日: 2023-04-26, 最終更新日: 2024-06-19)

主引用文献

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

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: 37189440
DOI: 10.3390/biom13040694

実験手法

X-RAY DIFFRACTION (2.2 Å)