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.
Int J Mol Sci. 2021 Jan 15;22(2):846. doi: 10.3390/ijms22020846.
Biomedically important histone lysine acetyltransferase KAT8 catalyses the acetyl coenzyme A-dependent acetylation of lysine on histone and other proteins. Here, we explore the ability of human KAT8 to catalyse the acetylation of histone H4 peptides possessing lysine and its analogues at position 16 (H4K16). Our synthetic and enzymatic studies on chemically and structurally diverse lysine mimics demonstrate that KAT8 also has a capacity to acetylate selected lysine analogues that possess subtle changes on the side chain and main chain. Overall, this work highlights that KAT8 has a broader substrate scope beyond natural lysine, and contributes to the design of new chemical probes targeting KAT8 and other members of the histone lysine acetyltransferase (KAT) family.
具有生物医学重要性的组蛋白赖氨酸乙酰转移酶 KAT8 催化乙酰辅酶 A 依赖性赖氨酸在组蛋白和其他蛋白质上的乙酰化。在这里，我们探索了人类 KAT8 催化具有赖氨酸及其在位置 16（H4K16）处类似物的组蛋白 H4 肽的乙酰化的能力。我们对化学和结构上多样化的赖氨酸类似物的合成和酶研究表明，KAT8 还具有乙酰化侧链和主链上具有细微变化的选定赖氨酸类似物的能力。总的来说，这项工作强调了 KAT8 除了天然赖氨酸之外还有更广泛的底物范围，并为针对 KAT8 和组蛋白赖氨酸乙酰转移酶 (KAT) 家族其他成员的新化学探针的设计做出了贡献。
