Probing lysine posttranslational modifications by unnatural amino acids

Posttranslational modifications, typically small chemical tags attached on amino acids following protein biosynthesis, have a profound effect on protein structure and function. Numerous chemically and structurally diverse posttranslational modifications, including methylation, acetylation, hydroxylation, and ubiquitination, have been identified and characterised on lysine residues in proteins. In this feature article, we focus on chemical tools that rely on the site-specific incorporation of unnatural amino acids into peptides and proteins to probe posttranslational modifications of lysine. We highlight that simple amino acid mimics enable detailed mechanistic and functional assignment of enzymes that install and remove such modifications, and proteins that specifically recognise lysine posttranslational modifications.

Automated summary

Posttranslational modifications have a significant impact on protein structure and function, with the incorporation of unnatural amino acids playing a crucial role in studying these modifications. Simple amino acid mimics enable detailed mechanistic and functional assignment of enzymes and proteins involved in these modifications.