Site-Selective Phosphoglycerate Mutase 1 Acetylation by a Small Molecule

作者：Xiaodan Zhang, Lulu Jiang, Ke Huang, Chuantao Fang, Jian Li, Jintong Yang, Huiti Li, Xiaoxue Ruan, Peng‐Hui Wang, Mingguang Mo, Ping Wu, Yanhui Xu, Chao Peng, Motonari Uesugi, Deyong Ye, Fa‐Xing Yu, Lu Zhou · 发表于：ACS Chemical Biology · 年份：2020 · DOI：10.1021/acschembio.9b00962 · 被引用次数：20 · 研究领域：Peptidase Inhibition and Analysis、Ubiquitin and proteasome pathways、Histone Deacetylase Inhibitors Research

Post-translational modifications play vital roles in fine-tuning a myriad of physiological processes, and one of the most important modifications is acetylation. Here, we report a ligand-directed site-selective acetylation using KHAc, a derivative of a phosphoglycerate mutase 1 (PGAM1) inhibitor. KHAc binds to PGAM1 and transfers its acetyl group to the ε-NH 2 of Lys100 to inactivate the enzyme. The acetyl transfer process was visualized by time-resolved crystallography, demonstrating that the transfer is driven by proximity effects. KHAc was capable of selectively and effectively acetylating Lys100 of PGAM1 in cultured human cells, accompanied by inhibited F-actin formation. Similar strategies could be used for exogenous control of other lysine post-translational modifications.