1. Structural Evidence of N6-Isopentenyladenosine As a New Ligand of Farnesyl Pyrophosphate Synthase
- Author
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Paola Picardi, Giuseppe Bifulco, Manuela Grimaldi, Maurizio Bifulco, Alessandra Tosco, Mario Scrima, Ettore Novellino, Anna Maria D'Ursi, Gianluigi Lauro, Raffaele Riccio, Sara Di Marino, Patrizia Gazzerro, Scrima, Mario, Lauro, Gianluigi, Grimaldi, Manuela, Di Marino, Sara, Tosco, Alessandra, Picardi, Paola, Gazzerro, Patrizia, Riccio, Raffaele, Novellino, Ettore, Bifulco, Maurizio, Bifulco, Giuseppe, and Maria D’Ursi, Anna
- Subjects
Virtual screening ,ATP synthase ,biology ,Protein Conformation ,Ligand ,Stereochemistry ,Drug Evaluation, Preclinical ,Farnesyl pyrophosphate ,Antineoplastic Agents ,Geranyltranstransferase ,Ligands ,Molecular Docking Simulation ,Isopentenyladenosine ,chemistry.chemical_compound ,Protein structure ,chemistry ,Biochemistry ,Drug Discovery ,biology.protein ,Humans ,Molecular Medicine ,Lead compound - 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.
- Published
- 2014