@Gallipoli with Prof. Toshimasa Itoh from Showa University of Tokyo
Our research activity focuses on the structural study of the nuclear receptors Peroxisome Proliferator-Activated Receptors (PPARs) that play a crucial role in the regulation of metabolic homeostasis. They can induce or repress genes involved in adipogenesis, lipid and glucose metabolism, energy balance, and inflammation.
Our research group contributed a great deal in this field evidencing new structural features of PPARs in the crystal complex with a new series of ligands that interact with different regions of the LBD. The conformational changes induced by ligands confer a differentiated biological response in cell and animal models, demonstrating a tight structural/functional relationship for PPAR ligands activity profile. Our interest is directed to both synthetic and natural molecules (such as resveratrol, betulinic acid and saponins) as safe candidates for the treatment of type 2 diabetes and metabolic disorders.
@Lecce with Prof. Keiko Yamamoto and Prof. Toshimasa Itoh from Showa University of Tokyo
Recently, through a multi-disciplinary approach, including NMR, SAXS, HDX and site-directed mutagenesis we focused on PPARγ conformational changes that impact CDK5 approaching, investigating the molecular basis for the inhibition of
Contact Person : GIORGIO POCHETTI
Tel : +39 0690672633
INVOLVED STAFF :
FACILITIES AND LABORATORIES :
Laboratory of Structural Biology
Access to Crystallization facility Robot Matrix E-drop at La Sapienza University (Dept. of Biochemistry) and to the diffraction beam-line facilities at synchrotron Elettra (Trieste) and ESRF (Grenoble).
GROUP RELATED RESEARCH PROJECTS :
- ACRAF 3 e ACRAF 4 “Crystallographic studies on the complexes of OXA-48 Beta Lactamase with new inhibitors”.
- Instruct Integrated Biology PID:1579 “Structural explanation of CDK5-mediated PPARg phosphorylation and its allosteric inhibition by PPARg small molecule modulators”.
- AIRC 2018 “A Structure-guided approach to target the Aurora-A/N-Myc complex in MYCN-amplified Neuroblastoma”.
GROUP RELATED PUBLICATIONS :
- Gloria Brusotti*, Roberta Montanari* , Davide Capelli , Giulia Cattaneo , Antonio Laghezza, Paolo Tortorella , Fulvio Loiodice, Franck Peiretti, Bernadette Bonardo, Alessandro Paiardini, EnricaCalleri (*equal contribution), “Betulinic acid is a PPARγ antagonist that hampers adipogenesis and promotes osteogenesis”, Scientific Reports 7(1), 5777 (2017).
- D.Capelli, C. Cerchia, R. Montanari, F. Loiodice, P. Tortorella, A., Laghezza, L. Cervoni, G. Pochetti and A. Lavecchia, “Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode” Scientific Reports 6: 34792 (2016).
- Roberta Montanari, Davide Capelli, Aldo Tava, Andrea Galli, Antonio Laghezza, Paolo Tortorella, Fulvio Loiodice & Giorgio Pochetti, “Screening of saponins and sapogenins from Medicago species as potential PPARγ agonists and X-ray structure of the complex PPARγ/caulophyllogenin” Scientific Reports 6: 27658 (2016).
- Lori, A. Pasquo, R. Montanari, D. Capelli, V. Consalvi, R. Chiaraluce, L. Cervoni, F. Loiodice, A. Laghezza, M. Aschi and G. Pochetti“Structural Basis of the Transactivation Deficiency of Human PPARg F360L Mutant Associated with Familial Partial Lipodystrophy” Acta Cryst D 70 1965-76 (2014).
- Montanari, R., Saccoccia, F., Scotti, E., Crestani, M., Godio, C., Gilardi, F., loiodice F. , Fracchiolla G., Laghezza A., Tortorella P., Lavecchia A., Novellino E., Mazza F., Aschi M., Pochetti, G. Crystal structure of the peroxisome proliferator-activated receptor gamma (ppargamma) ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design. Journal of Medicinal Chemistry, 51(24), 7768-7776 (2008).
Mentana, Rome, Dec 2010
Jesse Pinkman and Heisenberg @IC-SBL