5LSG

PPARgamma complex with the betulinic acid

Summary for 5LSG

• Entry DOI: 10.2210/pdb5lsg/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, Betulinic Acid (3 entities in total)
• Functional Keywords: antagonist, complex, transcription factor, nuclear receptor, signaling protein
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 69620.50

Authors

Pochetti, G.,Montanari, R.,Capelli, D.,Loiodice, F.,Laghezza, A.,Calleri, E.,Paiardini, A. (deposition date: 2016-08-26, release date: 2017-08-09, Last modification date: 2024-01-17)

Primary citation

Brusotti, G.,Montanari, R.,Capelli, D.,Cattaneo, G.,Laghezza, A.,Tortorella, P.,Loiodice, F.,Peiretti, F.,Bonardo, B.,Paiardini, A.,Calleri, E.,Pochetti, G.
Betulinic acid is a PPAR gamma antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis.
Sci Rep, 7:5777-5777, 2017

PubMed Abstract: PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, and they serve as an alternative treatment for metabolic diseases. In this work, an affinity-based bioassay was found to be effective for selecting PPAR ligands from the dried extract of an African plant (Diospyros bipindensis). Among the ligands, we identified betulinic acid (BA), a compound already known for its anti-inflammatory, anti-tumour and antidiabetic properties, as a PPARγ and PPARα antagonist. Cell differentiation assays showed that BA inhibits adipogenesis and promotes osteogenesis; either down-regulates or does not affect the expression of a series of adipogenic markers; and up-regulates the expression of osteogenic markers. Moreover, BA increases basal glucose uptake in 3T3-L1 adipocytes. The crystal structure of the complex of BA with PPARγ sheds light, at the molecular level, on the mechanism by which BA antagonizes PPARγ, and indicates a unique binding mode of this antagonist type. The results of this study show that the natural compound BA could be an interesting and safe candidate for the treatment of type 2 diabetes and bone diseases.

PubMed: 28720829
DOI: 10.1038/s41598-017-05666-6

Experimental method

X-RAY DIFFRACTION (2 Å)