jm061213n_si_001.pdf (1.63 MB)
Small Molecule Inhibitors of Histone Arginine Methyltransferases: Homology Modeling, Molecular Docking, Binding Mode Analysis, and Biological Evaluations
journal contribution
posted on 2007-03-22, 00:00 authored by Rino Ragno, Silvia Simeoni, Sabrina Castellano, Caterina Vicidomini, Antonello Mai, Antonella Caroli, Anna Tramontano, Claudia Bonaccini, Patrick Trojer, Ingo Bauer, Gerald Brosch, Gianluca SbardellaThe screening of the inhibition capabilities of dye-like small molecules from a focused library against both
human PRMT1 and Aspergillus nidulans RmtA is reported as well as molecular modeling studies (homology
modeling, molecular docking, and 3-D QSAR) of the catalytic domain of the PRMT1 fungal homologue
RmtA. The good correlation between computational and biological results makes RmtA a reliable tool for
screening arginine methyltransferase inhibitors. In addition, the binding mode analyses of tested derivatives
reveal the crucial role of two regions, the pocket formed by Ile12, His13, Met16, and Thr49 and the SAM
cisteinic binding site subsite. These regions should be taken into account in the design of novel PRMT
inhibitors.