cb9b00962_si_001.pdf (1.7 MB)
Site-Selective Phosphoglycerate Mutase 1 Acetylation by a Small Molecule
journal contribution
posted on 2020-02-24, 17:03 authored by Xiaodan Zhang, Lulu Jiang, Ke Huang, Chuantao Fang, Jian Li, Jintong Yang, Huiti Li, Xiaoxue Ruan, Penghui Wang, Mingguang Mo, Ping Wu, Yanhui Xu, Chao Peng, Motonari Uesugi, Deyong Ye, Fa-Xing Yu, Lu ZhouPost-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-NH2 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.