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ID: ALA4138076

Journal: Eur J Med Chem

Title: Methyllysine binding domains: Structural insight and small molecule probe development.

Authors: Teske KA, Hadden MK.

Abstract: A frequent posttranslational modification that regulates gene expression is the mono-, di-, and/or tri- methylation of lysine residues on the histone tails of chromatin. The recognition of methylated lysine marks is facilitated by specific reader proteins that contain a methyllysine binding domain. This class of reader proteins has emerged as a focus of epigenetic research due to its crucial role in gene regulation, oncogenesis and other disease pathways. The design and synthesis of small molecules that target these domains and disrupt reader/histone protein-protein interactions have demonstrated the druggability of methyllysine binding pockets and provided preliminary evidence that their disruption holds therapeutic potential. In this review, we detail the structures of methyllysine binding domains, highlight the primary roles of these reader proteins in both normal and disease states, and describe the current status of small molecule development against these emerging epigenetic regulators.

CiteXplore: 28478342

DOI: 10.1016/j.ejmech.2017.04.047