一种组蛋白去甲基化酶 Jumonji C 结构域包含蛋白的细胞功能的选择性抑制剂和探针。
A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases.
机构信息
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.
出版信息
J Am Chem Soc. 2011 Jun 22;133(24):9451-6. doi: 10.1021/ja201597b. Epub 2011 May 31.
Abstract
Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic imprinting. Histone demethylases are the most recent family of histone-modifying enzymes discovered. Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The inhibitor derives from a structure-based design and preferentially inhibits the subfamily of trimethyl lysine demethylases. Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing his-tone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in epigenetics.
摘要
组蛋白甲基化是调控基因表达、基因组稳定性、DNA 修复和基因组印记的重要染色质标记。组蛋白去甲基化酶是最近发现的组蛋白修饰酶家族。在这里，我们报告了一种小分子 Jumonji C 结构域组蛋白去甲基化酶抑制剂的特性。该抑制剂来源于基于结构的设计，优先抑制三甲基赖氨酸去甲基酶亚家族。其甲酯前药甲基stat 在细胞中选择性抑制 Jumonji C 结构域组蛋白去甲基化酶，可能是研究染色质及其在表观遗传学中作用的有用小分子探针。
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