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Lysine Ethylation by Histone Lysine Methyltransferases
Author(s) -
Al Temimi Abbas H. K.,
Martin Michael,
Meng Qingxi,
Lenstra Danny C.,
Qian Ping,
Guo Hong,
Weinhold Elmar,
Mecinović Jasmin
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900359
Subject(s) - lysine , methyltransferase , histone , chemistry , biochemistry , histone methyltransferase , histone h3 , methylation , stereochemistry , amino acid , dna
Biomedicinally important histone lysine methyltransferases (KMTs) catalyze the transfer of a methyl group from S ‐adenosylmethionine (AdoMet) cosubstrate to lysine residues in histones and other proteins. Herein, experimental and computational investigations on human KMT‐catalyzed ethylation of histone peptides by using S ‐adenosylethionine (AdoEth) and Se ‐adenosylselenoethionine (AdoSeEth) cosubstrates are reported. MALDI‐TOF MS experiments reveal that, unlike monomethyltransferases SETD7 and SETD8, methyltransferases G9a and G9a‐like protein (GLP) do have the capacity to ethylate lysine residues in histone peptides, and that cosubstrates follow the efficiency trend AdoMet>AdoSeEth>AdoEth. G9a and GLP can also catalyze AdoSeEth‐mediated ethylation of ornithine and produce histone peptides bearing lysine residues with different alkyl groups, such as H3K9meet and H3K9me2et. Molecular dynamics and free energy simulations based on quantum mechanics/molecular mechanics potential supported the experimental findings by providing an insight into the geometry and energetics of the enzymatic methyl/ethyl transfer process.