Distinct specificities of the HEMK2 protein methyltransferase in methylation of glutamine and lysine residues.

ABSTRACT: The HEMK2 protein methyltransferase has been described as glutamine methyltransferase catalyzing ERF1-Q185me1 and lysine methyltransferase catalyzing H4K12me1. Methylation of two distinct target residues is unique for this class of enzymes. To understand the specific catalytic adaptations of HEMK2 allowing it to master this chemically challenging task, we conducted a detailed investigation of the substrate sequence specificities of HEMK2 for Q- and K-methylation. Our data show that HEMK2 prefers methylation of Q over K at peptide and protein level. Moreover, the ERF1 sequence is strongly preferred as substrate over the H4K12 sequence. With peptide SPOT array methylation experiments, we show that Q-methylation preferentially occurs in a G-Q-X₃ -R context, while K-methylation pref

SUBMITTER: Weirich S 

PROVIDER: S-EPMC10804810 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature