Abstract
Structural modules that specifically recognize—or read—methylated or acetylated lysine residues on histone peptides are important components of chromatin-mediated signaling and epigenetic regulation of gene expression. Deregulation of epigenetic mechanisms is associated with disease conditions, and antagonists of acetyl-lysine binding bromodomains are efficacious in animal models of cancer and inflammation, but little is known regarding the druggability of methyl-lysine binding modules. We conducted a systematic structural analysis of readers of methyl marks and derived a predictive druggability landscape of methyl-lysine binding modules. We show that these target classes are generally less druggable than bromodomains, but that some proteins stand as notable exceptions.
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The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from Canadian Institutes for Health Research, Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Eli Lilly, Pfizer, Novartis Research Foundation, Life Technologies, Ontario Innovation Trust, Ontario Ministry for Research and Innovation, and Wellcome Trust.
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Santiago, C., Nguyen, K. & Schapira, M. Druggability of methyl-lysine binding sites. J Comput Aided Mol Des 25, 1171–1178 (2011). https://doi.org/10.1007/s10822-011-9505-2
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DOI: https://doi.org/10.1007/s10822-011-9505-2