Lysine residues in proteins and peptides (Lys)

Lysine residues are basic, positively charged amino acids that serve as critical structural and functional components within proteins and peptides (UniProt, 2024). They are uniquely characterized by a nucleophilic epsilon-amino group, which acts as a versatile platform for numerous post-translational modifications (PTMs), including acetylation, methylation, ubiquitination, and sumoylation (NCBI, 2023). These modifications are central to the regulation of gene expression, protein stability, and cellular signaling pathways. While lysine residues as a collective group do not constitute a single therapeutic target, they are the focal point for several major drug classes, including epigenetic inhibitors that target the enzymes modifying these residues, such as HDACs and KMTs (Dalton et al., Nature Reviews Chemistry, 2020). Additionally, the chemical reactivity of lysine is frequently exploited in the development of antibody-drug conjugates (ADCs) like Trastuzumab emtansine and targeted covalent inhibitors (Gehringer & Laufer, J. Med. Chem., 2019). Dysregulation of lysine-associated PTMs is a hallmark of many diseases, particularly oncology and neurodegeneration, making the study of these residues vital for modern drug discovery.

Other names

L-lysine residuesLysyl residuesK residuesEpsilon-amino group of lysineProtein lysine

Covalent bioconjugation to the epsilon-amino group of lysine residues; Inhibition of enzymes (e.g., HDACs, KMTs, KDMs) that regulate the post-translational modification status of lysine residues (Dalton et al., 2020).