The Chemical Biology of Reversible Lysine Post-translational Modifications

Lysine (Lys) residues in proteins undergo a wide range of reversible post-translational modifications (PTMs), which can regulate enzyme activities, chromatin structure, protein-protein interactions, protein stability, and cellular localization. Here we discuss the “writers,” “erasers,” and “readers” of some of the common protein Lys PTMs and summarize examples of their major biological impacts. We also review chemical biology approaches, from small-molecule probes to protein chemistry technologies, that have helped to delineate Lys PTM functions and show promise for a diverse set of biomedical applications. [Display omitted] Zhipeng Wang and Philip Cole review major types of chemical modifications of the amino acid lysine in proteins and how they are added and removed. They also discuss a number of chemical approaches and how they have been applied to clarify the roles of lysine modifications in biology and medicine.