Dataset Information

Lysine Ethylation by Histone Lysine Methyltransferases.

ABSTRACT: 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.

SUBMITTER: Al Temimi AHK

PROVIDER: S-EPMC7064923 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Lysine Ethylation by Histone Lysine Methyltransferases.

Al Temimi Abbas H K AHK Martin Michael M Meng Qingxi Q Lenstra Danny C DC Qian Ping P Guo Hong H Weinhold Elmar E Mecinović Jasmin J

Chembiochem : a European journal of chemical biology 20191024 3

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 SET ...[more]

PMID: 31287209

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Project description:Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites.

Dataset Information

Lysine Ethylation by Histone Lysine Methyltransferases.

Publications

Lysine Ethylation by Histone Lysine Methyltransferases.

Similar Datasets

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