Drug Discovery Toward Antagonists of Methyl-Lysine Binding Proteins
J. Martin Herold, Lindsey A Ingerman, Cen Gao, Stephen V Frye*
Identifiers and Pagination:Year: 2011
Issue: Suppl 1
First Page: 51
Last Page: 61
Publisher Id: CCGTM-5-51
Article History:Received Date: 26/1/2011
Revision Received Date: 22/2/2011
Acceptance Date: 25/4/2011
Electronic publication date: 22/8/2011
Collection year: 2011
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
The recognition of methyl-lysine and -arginine residues on both histone and other proteins by specific “reader” elements is important for chromatin regulation, gene expression, and control of cell-cycle progression. Recently the crucial role of these reader proteins in cancer development and dedifferentiation has emerged, owing to the increased interest among the scientific community. The methyl-lysine and -arginine readers are a large and very diverse set of effector proteins and targeting them with small molecule probes in drug discovery will inevitably require a detailed understanding of their structural biology and mechanism of binding. In the following review, the critical elements of methyl-lysine and -arginine recognition will be summarized with respect to each protein family and initial results in assay development, probe design, and drug discovery will be highlighted.