Zucconi Beth E, Cole Philip A
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA.
Curr Opin Chem Biol. 2017 Aug;39:109-115. doi: 10.1016/j.cbpa.2017.05.015. Epub 2017 Jul 6.
Epigenetic enzymes including histone modifying enzymes are key regulators of gene expression in normal and disease processes. Many drug development strategies to target histone modifying enzymes have focused on ligands that bind to enzyme active sites, but allosteric pockets offer potentially attractive opportunities for therapeutic development. Recent biochemical studies have revealed roles for small molecule and peptide ligands binding outside of the active sites in modulating the catalytic activities of histone modifying enzymes. Here we highlight several examples of allosteric regulation of epigenetic enzymes and discuss the biological significance of these findings.
包括组蛋白修饰酶在内的表观遗传酶是正常和疾病过程中基因表达的关键调节因子。许多针对组蛋白修饰酶的药物开发策略都集中在与酶活性位点结合的配体上，但别构口袋为治疗开发提供了潜在的诱人机会。最近的生化研究揭示了小分子和肽配体在活性位点之外结合对调节组蛋白修饰酶催化活性的作用。在这里，我们重点介绍表观遗传酶别构调节的几个例子，并讨论这些发现的生物学意义。
