Fine-tuning of lysine side chain modulates the activity of histone lysine methyltransferases.

ABSTRACT: Histone lysine methyltransferases (KMTs) play an important role in epigenetic gene regulation and have emerged as promising targets for drug discovery. However, the scope and limitation of KMT catalysis on substrates possessing substituted lysine side chains remain insufficiently explored. Here, we identify new unnatural lysine analogues as substrates for human methyltransferases SETD7, SETD8, G9a and GLP. Two synthetic amino acids that possess a subtle modification on the lysine side chain, namely oxygen at the γ position (K_O, oxalysine) and nitrogen at the γ position (K_N, azalysine) were incorporated into histone peptides and tested as KMTs substrates. Our results demonstrate that these lysine analogues are mono-, di-, and trimethylated to a different extent by trim

SUBMITTER: Al Temimi AHK 

PROVIDER: S-EPMC7726145 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature