The research activities of Dr. Giuseppina De Simone are focused on several aspects of structure/function relationships in macromolecules with a biological interest. These studies have been dedicated to a variety of macromolecular systems with different structural complexities and have been carried out by combining X-ray crystallographic methods with several other techniques, including enzyme expression and purification, enzyme functional characterization, molecular modelling, kinetic and spectroscopic analysis. Over the last ten years, in collaboration with a framework of international institutions, her research has been mainly dedicated to the structural characterization of enzymes involved in human diseases as well as the design/characterization of small molecules able to modulate their activity. Dr. De Simone is author of 120 scientific publications on international journals among which PNAS, Nat Cell Biol, JACS, Chem. Rev. She has been the Principal Investigator of several research grants from national (CNR; Regione Campania) and international (EU, Solvay Pharmaceuticals) institutions.
Structural Biology, Drug design, Biocrystallography
Proteomics, Cellular Biology
Hydroxylamine-O-sulfonamide is a versatile lead compound for the development of carbonic anhydrase inhibitors. Di Fiore A, Vergara A, Caterino M, Alterio V, Monti SM, Ombouma J, Dumy P, Vullo D, Supuran CT, Winum JY, De Simone G. Chem Commun (Camb). 2015 Jul 21;51(57):11519-22.
Characterization of carbonic anhydrase IX interactome reveals proteins assisting its nuclear localization in hypoxic cells. Buanne P, Renzone G, Monteleone F, Vitale M, Monti SM, Sandomenico A, Garbi C, Montanaro D, Accardo M, Troncone G, Zatovicova M, Csaderova L, Supuran CT, Pastorekova S, Scaloni A, De Simone G, Zambrano N. J Proteome Res. 2013 Jan 4;12(1):282-92.
Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Alterio V, Di Fiore A, D'Ambrosio K, Supuran CT, De Simone G. Chem Rev. 2012 Aug 8;112(8):4421-68.
Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX. Alterio V, Hilvo M, Di Fiore A, Supuran CT, Pan P, Parkkila S, Scaloni A, Pastorek J, Pastorekova S, Pedone C, Scozzafava A, Monti SM, De Simone G. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16233-8.
Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. Canettieri G, Di Marcotullio L, Greco A, Coni S, Antonucci L, Infante P, Pietrosanti L, De Smaele E, Ferretti E, Miele E, Pelloni M, De Simone G, Pedone EM, Gallinari P, Giorgi A, Steinkühler C, Vitagliano L, Pedone C, Schinin ME, Screpanti I, Gulino A. Nat Cell Biol. 2010 Feb;12(2):132-42.