Lysine Possesses the Optimal Chain Length for Histone Lysine Methyltransferase Catalysis
| Autor: | Jasmin Mecinović, Y. Vijayendar Reddy, Abbas H. K. Al Temimi, Paul B. White, Hong Guo, Ping Qian |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
S-Adenosylmethionine Magnetic Resonance Spectroscopy Methyltransferase Lysine lcsh:Medicine Synthetic Organic Chemistry Article Catalysis 03 medical and health sciences chemistry.chemical_compound Humans Histone octamer lcsh:Science GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Multidisciplinary biology lcsh:R Histone-Lysine N-Methyltransferase Methylation Ornithine Bromodomain 030104 developmental biology Histone chemistry Biochemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Histone methyltransferase biology.protein lcsh:Q |
| Zdroj: | Scientific Reports Scientific Reports, 7, 1-12 Scientific Reports, 7, pp. 1-12 Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-16128-4 |
| Popis: | Histone lysine methyltransferases (KMTs) represent an important class of epigenetic enzymes that play essential roles in regulation of gene expression in humans. Members of the KMT family catalyze the transfer of the methyl group from S-adenosylmethionine (SAM) to lysine residues in histone tails and core histones. Here we report combined MALDI-TOF MS experiments, NMR analyses and quantum mechanical/molecular dynamics studies on human KMT-catalyzed methylation of the most related shorter and longer lysine analogues, namely ornithine and homolysine, in model histone peptides. Our experimental work demonstrates that while lysine is an excellent natural substrate for KMTs, ornithine and homolysine are not. This study reveals that ornithine does not undergo KMT-catalyzed methylation reactions, whereas homolysine can be methylated by representative examples of human KMTs. The results demonstrate that the specificity of KMTs is highly sensitive to the side chain length of the residue to be methylated. The origin for the degree of the observed activities of KMTs on ornithine and homolysine is discussed. |
| Databáze: | OpenAIRE |
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