Anup K Upadhyay, Russell A Judge, Leiming Li, Ron Pithawalla, Justin Simanis, Pierre M Bodelle, Violeta L Marin, Rodger F Henry, Andrew M Petros, Chaohong Sun
The tandem TUDOR domains present in the non-catalytic C-terminal half of the KDM4A, 4B and 4C enzymes play important roles in regulating their chromatin localizations and substrate specificities. They achieve this regulatory role by binding to different tri-methylated lysine residues on histone H3 (H3-K4me3, H3-K23me3) and histone H4 (H4-K20me3) depending upon the specific chromatin environment. In this work, we have used a 2D-NMR based fragment screening approach to identify a novel fragment (1a), which binds to the KDM4A-TUDOR domain and shows modest competition with H3-K4me3 binding in biochemical as well as in vitro cell based assays...
April 19, 2018: Bioorganic & Medicinal Chemistry Letters