Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan.
College of Pharmacy, University of Georgia, Athens, GA, 30602, USA.
Cell Mol Life Sci. 2019 Aug;76(15):2917-2932. doi: 10.1007/s00018-019-03145-x. Epub 2019 May 23.
Protein arginine methyltransferases (PRMTs) catalyze the methyl transfer to the arginine residues of protein substrates and are classified into three major types based on the final form of the methylated arginine. Recent studies have shown a strong correlation between PRMT expression level and the prognosis of cancer patients. Currently, crystal structures of eight PRMT members have been determined. Kinetic and structural studies have shown that all PRMTs share similar, but unique catalytic and substrate recognition mechanism. In this review, we discuss the structural similarities and differences of different PRMT members, focusing on their overall structure, S-adenosyl-L-methionine-binding pocket, substrate arginine recognition and catalytic mechanisms. Since PRMTs are valuable targets for drug discovery, we also rationally classify the known PRMT inhibitors into five classes and discuss their mechanisms of action at the atomic level.
蛋白精氨酸甲基转移酶（PRMTs）催化将甲基转移到蛋白质底物的精氨酸残基上，并根据甲基化精氨酸的最终形式分为三大类。最近的研究表明，PRMT 的表达水平与癌症患者的预后有很强的相关性。目前已经确定了 8 个 PRMT 成员的晶体结构。动力学和结构研究表明，所有 PRMT 都具有相似但独特的催化和底物识别机制。在这篇综述中，我们讨论了不同 PRMT 成员的结构相似性和差异性，重点讨论了它们的整体结构、S-腺苷甲硫氨酸结合口袋、底物精氨酸识别和催化机制。由于 PRMTs 是药物发现的有价值的靶点，我们还将已知的 PRMT 抑制剂合理地分为五类，并在原子水平上讨论它们的作用机制。
