组蛋白赖氨酸甲基转移酶的别构调控：从特定环境的调控到选择性药物。

Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.

EMBL-Australia and the ARC Centre of Excellence in Advanced Molecular Imaging, Clayton, Victoria, Australia.

Biochem Soc Trans. 2021 Apr 30;49(2):591-607. doi: 10.1042/BST20200238.

Histone lysine methyltransferases (HKMTs) are key regulators of many cellular processes. By definition, HKMTs catalyse the methylation of lysine residues in histone proteins. The enzymatic activities of HKMTs are under precise control, with their allosteric regulation emerging as a prevalent paradigm. We review the molecular mechanisms of allosteric regulation of HKMTs using well-studied histone H3 (K4, K9, K27 and K36) methyltransferases as examples. We discuss the current advances and future potential in targeting allosteric sites of HKMTs for drug development.

组蛋白赖氨酸甲基转移酶（HKMTs）是许多细胞过程的关键调节因子。根据定义，HKMTs 催化组蛋白蛋白赖氨酸残基的甲基化。HKMTs 的酶活性受到精确控制，其变构调节成为一种流行的范例。我们使用经过充分研究的组蛋白 H3（K4、K9、K27 和 K36）甲基转移酶作为例子，综述了 HKMTs 的变构调节的分子机制。我们讨论了针对 HKMTs 的变构位点进行药物开发的当前进展和未来潜力。