Institute of Crystallography - CNR

Structural analysis of proteins and protein-ligand complexes

The structural analysis of proteins and protein-ligand complexes aims to understand the molecular mechanisms that make cells non-functional when diseases affect humans and to study new molecules capable of restoring their functionality.

The research activity conducted in the field of Structural Biology, through an integrated approach between physical, chemical, biological and bioinformatics methods, has as its purpose i) the development of new drugs and the elucidation of the molecular mechanisms necessary to make a cell functional and ii) understand how these processes are regulated in pathological conditions.
To this end we use genetic engineering techniques to express recombinant proteins from E.Coli and chromatographic methodologies (FPLC) for their purification. The purified proteins are crystallized and used, alone or together with other proteins or synthetic molecules, for crystallographic studies carried out at the European synchrotron facilities. The collected data are then processed and analyzed to obtain details on the functioning mechanisms of the proteins or for the optimization of the synthetic molecules. In our laboratory we have an integrated approach and the structural data are completed with complementary investigations such as affinity analyzes carried out through the use of Surface Plasmon Resonance, biochemical and bioinformatic analyzes which aim to obtain a broader view of the processes studied. In this context, as part of funded projects, we have dealt with the study of multiple proteins such as PPARα, γ and δ, MMP-2, MMP-8, MMP-9, β-catenin, CDK5, AKT1, OXA-48.

Reference works

– Montanari, R., Capelli, D., Yamamoto, K., Awaishima, H., Nishikata, K., Barendregt, A., Heck, A.J.R., Loiodice, F., Altieri, F., Paiardini, A., Grottesi, A., Pirone, L., Pedone, E., Peiretti, F., Brunel, J.M., Itoh, T., Pochetti, G. Insights into pparγphosphorylation and its inhibition mechanism (2020) Journal of Medicinal Chemistry.
– 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 γbinding Properties and Biological Activities (2020) Journal of Medicinal Chemistry.
– Dalila Boi, Fani Souvalidou, Roberta Montanari, Federica Polverino, Grazia Marini, Davide Capelli, Giorgio Pochetti, Angela Tramonti, Roberto Contestabile, Daniela Trisciuoglio, Patrizia Carpinelli, Camilla Ascanelli, Catherine Lindon, Alessandro De Leo, Michele Saviano, Roberto Di Santo, Roberta Costi, Giulia Guarguaglini, Alessandro Paiardini, PHA-680626 is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc, International Journal of Molecular Sciences (2021).
– Spizzichino S., Boi D., Boumis G., Lucchi R., Liberati F.R., Capelli D., Montanari R., Pochetti G., Piacentini R., Parisi G. Paone A., Rinaldo S., Contestabile., Tramonti A., Paiardini A., Giardina G., Cutruzzolà F., Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex (2021) Febs Journal FJ-21-0863.