title: Structural evidence of N6-isopentenyladenosine as a new ligand of farnesyl pyrophosphate synthase.
abstract: N6-isopentenyladenosine (i6A), a modified nucleoside belonging to the cytokinin family, has shown in humans many biological actions, including antitumoral effects through the modulation of the farnesyl pyrophosphate synthase (FPPS) activity. To investigate the relationship between i6A and FPPS, we undertook an inverse virtual screening computational target searching, testing i6A on a large panel of 3D protein structures involved in cancer processes. Experimentally, we performed an NMR investigation of i6A in the presence of FPPS protein. Both inverse virtual screening and saturation transfer difference (STD) NMR outcomes provided evidence of the structural interaction between i6A and FPPS, pointing to i6A as a valuable lead compound in the search of new ligands endowed with antitumoral potential and targeting FPPS protein.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scrima
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Lauro
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Sara
authors.initials: S
authors.lastname: Di Marino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tosco
authors.forename: Paola
authors.initials: P
authors.lastname: Picardi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gazzerro
authors.forename: Raffaele
authors.initials: R
authors.lastname: Riccio
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bifulco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D051228:Geranyltranstransferase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007541:Isopentenyladenosine / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D062105:Molecular Docking Simulation; D011487:Protein Conformation
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D007541:Isopentenyladenosine; D051228:Geranyltranstransferase