Author:
Temimi Abbas H. K. Al,Tran Vu,Teeuwen Ruben S.,Altunc Arthur J.,Amatdjais-Groenen Helene I. V.,White Paul B.,Lenstra Danny C.,Proietti Giordano,Wang Yali,Wegert Anita,Blaauw Richard H.,Qian Ping,Ren Wansheng,Guo Hong,Mecinović Jasmin
Abstract
AbstractMethylation of lysine residues in histone proteins is catalyzed by S-adenosylmethionine (SAM)-dependent histone lysine methyltransferases (KMTs), a genuinely important class of epigenetic enzymes of biomedical interest. Here we report synthetic, mass spectrometric, NMR spectroscopic and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics studies on KMT-catalyzed methylation of histone peptides that contain lysine and its sterically demanding analogs. Our synergistic experimental and computational work demonstrates that human KMTs have a capacity to catalyze methylation of slightly bulkier lysine analogs, but lack the activity for analogs that possess larger aromatic side chains. Overall, this study provides an important chemical insight into molecular requirements that contribute to efficient KMT catalysis and expands the substrate scope of KMT-catalyzed methylation reactions.
Publisher
Springer Science and Business Media LLC
Cited by
8 articles.
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