Boriack-Sjodin P Ann, Swinger Kerren K
Epizyme, Inc. , 400 Technology Square, Cambridge, Massachusetts 02139, United States.
Biochemistry. 2016 Mar 22;55(11):1557-69. doi: 10.1021/acs.biochem.5b01129. Epub 2015 Dec 22.
Methyltransferase proteins make up a superfamily of enzymes that add one or more methyl groups to substrates that include protein, DNA, RNA, and small molecules. The subset of proteins that act upon arginine and lysine side chains are characterized as epigenetic targets because of their activity on histone molecules and their ability to affect transcriptional regulation. However, it is now clear that these enzymes target other protein substrates, as well, greatly expanding their potential impact on normal and disease biology. Protein methyltransferases are well-characterized structurally. In addition to revealing the overall architecture of the subfamilies of enzymes, structures of complexes with substrates and ligands have permitted detailed analysis of biochemical mechanism, substrate recognition, and design of potent and selective inhibitors. This review focuses on how knowledge gained from structural studies has impacted the understanding of this large class of epigenetic enzymes.
甲基转移酶蛋白构成了一个酶的超家族，该家族会将一个或多个甲基添加到底物上，这些底物包括蛋白质、DNA、RNA和小分子。作用于精氨酸和赖氨酸侧链的蛋白质子集因其对组蛋白分子的活性以及影响转录调控的能力而被视为表观遗传靶点。然而，现在很清楚的是，这些酶也作用于其他蛋白质底物，极大地扩展了它们对正常生物学和疾病生物学的潜在影响。蛋白质甲基转移酶在结构上已得到充分表征。除了揭示酶亚家族的整体结构外，与底物和配体形成的复合物的结构还允许对生化机制、底物识别以及强效和选择性抑制剂的设计进行详细分析。本综述重点关注从结构研究中获得的知识如何影响对这类大型表观遗传酶的理解。
