title: Structural aspects of small-molecule inhibition of methyllysine reader proteins.
abstract: Methyl reader proteins recognize and bind to post-translationally methylated residues. They execute the commands issued by protein methyltransferases and play functional roles in diverse cellular processes including gene regulation, development and oncogenesis. Efforts to inhibit these proteins are relatively new. Only a small number of methyl reader proteins belonging to the chromodomain, malignant brain tumor domain, plant homeodomain finger and Tudor domain families have been targeted by chemical inhibitors. This review summarizes inhibitors that have been reported to date, and provides a perspective for future progress. Structural determinants for methyl reader inhibition will be presented, along with an analysis of the molecular interactions that control potency and selectivity for inhibitors of each family.
authors: Department of Chemistry, University of Victoria, Victoria, BC, V8W 3V6 Canada.
authors: Natalia
authors: N
authors: Milosevich
authors: Department of Chemistry, University of Victoria, Victoria, BC, V8W 3V6 Canada.
authors: Zoey
authors: Z
authors: Warmerdam
authors: Department of Chemistry, University of Victoria, Victoria, BC, V8W 3V6 Canada.
authors: Fraser
authors: F
authors: Hof
mesh_terms: D000818:Animals; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D000072417:Protein Domains / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D054852:Small Molecule Libraries; D008239:Lysine
keywords: aromatic cage; epigenetics; methyllysine reader proteins; post-translational methylation; small-molecule inhibitors