Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark.
Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.
Sci Rep. 2020 Aug 3;10(1):13046. doi: 10.1038/s41598-020-69510-0.
Histone lysine acetyltransferase (KAT)-catalyzed acetylation of lysine residues in histone tails plays a key role in regulating gene expression in eukaryotes. Here, we examined the role of lysine side chain length in the catalytic activity of human KATs by incorporating shorter and longer lysine analogs into synthetic histone H3 and H4 peptides. The enzymatic activity of MOF, PCAF and GCN5 acetyltransferases towards histone peptides bearing lysine analogs was evaluated using MALDI-TOF MS assays. Our results demonstrate that human KAT enzymes have an ability to catalyze an efficient acetylation of longer lysine analogs, whereas shorter lysine analogs are not substrates for KATs. Kinetics analyses showed that lysine is a superior KAT substrate to its analogs with altered chain length, implying that lysine has an optimal chain length for KAT-catalyzed acetylation reaction.
组蛋白赖氨酸乙酰转移酶（KAT）催化组蛋白尾部赖氨酸残基的乙酰化在真核生物中调节基因表达中起着关键作用。在这里，我们通过将较短和较长的赖氨酸类似物掺入合成组蛋白 H3 和 H4 肽中来检查赖氨酸侧链长度在人类 KAT 催化活性中的作用。使用 MALDI-TOF MS 测定法评估了 MOF、PCAF 和 GCN5 乙酰转移酶对带有赖氨酸类似物的组蛋白肽的酶活性。我们的结果表明，人类 KAT 酶能够有效地催化较长赖氨酸类似物的乙酰化，而较短的赖氨酸类似物则不是 KAT 的底物。动力学分析表明，赖氨酸是 KAT 优于其具有改变链长的类似物的底物，这意味着赖氨酸具有 KAT 催化的乙酰化反应的最佳链长。
