Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands.
Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, USA.
Sci Rep. 2017 Nov 23;7(1):16148. doi: 10.1038/s41598-017-16128-4.
Histone lysine methyltransferases (KMTs) represent an important class of epigenetic enzymes that play essential roles in regulation of gene expression in humans. Members of the KMT family catalyze the transfer of the methyl group from S-adenosylmethionine (SAM) to lysine residues in histone tails and core histones. Here we report combined MALDI-TOF MS experiments, NMR analyses and quantum mechanical/molecular dynamics studies on human KMT-catalyzed methylation of the most related shorter and longer lysine analogues, namely ornithine and homolysine, in model histone peptides. Our experimental work demonstrates that while lysine is an excellent natural substrate for KMTs, ornithine and homolysine are not. This study reveals that ornithine does not undergo KMT-catalyzed methylation reactions, whereas homolysine can be methylated by representative examples of human KMTs. The results demonstrate that the specificity of KMTs is highly sensitive to the side chain length of the residue to be methylated. The origin for the degree of the observed activities of KMTs on ornithine and homolysine is discussed.
组蛋白赖氨酸甲基转移酶（KMTs）是一类重要的表观遗传酶，在人类基因表达调控中发挥着重要作用。KMT 家族成员催化 S-腺苷甲硫氨酸（SAM）的甲基转移到组蛋白尾部和核心组蛋白赖氨酸残基上。在这里，我们报告了 MALDI-TOF MS 实验、NMR 分析和量子力学/分子动力学研究，研究了人类 KMT 催化的模型组蛋白肽中最相关的较短和较长赖氨酸类似物精氨酸和同赖氨酸的甲基化。我们的实验工作表明，虽然赖氨酸是 KMT 的极好天然底物，但精氨酸和同赖氨酸不是。这项研究表明，精氨酸不会发生 KMT 催化的甲基化反应，而同赖氨酸可以被代表性的人类 KMT 甲基化。结果表明，KMT 的特异性对要甲基化的残基侧链长度非常敏感。讨论了观察到的 KMTs 对精氨酸和同赖氨酸活性程度的起源。
