Lysine Possesses the Optimal Chain Length for Histone Lysine Methyltransferase Catalysis

Temimi, Abbas H.  K.  Al; Reddy, Y. Vijayendar; White, Paul B.; Guo, Hong; Qian, Ping; Mecinović, Jasmin

doi:10.1038/s41598-017-16128-4

Lysine Possesses the Optimal Chain Length for Histone Lysine Methyltransferase Catalysis

Journal Article · Thu Nov 23 00:00:00 EST 2017 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-017-16128-4· OSTI ID:1624363

^[1]; Reddy, Y. Vijayendar ^[2]; White, Paul B. ^[2]; Guo, Hong ^[3]; Qian, Ping ^[4]; Mecinović, Jasmin ^[2]

Radboud Univ., Nijmegen, (The Netherlands). Inst. for Molecules and Materials; DOE/OSTI
Radboud Univ., Nijmegen, (The Netherlands). Inst. for Molecules and Materials
Univ. of Tennessee, Knoxville, (United States). Department of Biochemistry and Cellular and Molecular Biology; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). UT/ORNL Center for Molecular Biophysics
Shandong Agricultural Univ., Taian (China)

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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Lab (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: China Scholarship Council; National Natural Science Foundation of China; National Science Foundation (NSF); Natural Science Foundation of Shandong Province; Netherlands Organization for Scientific Research; USDOE Office of Science (SC)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1624363

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 7; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Examining sterically demanding lysine analogs for histone lysine methyltransferase catalysis Temimi, Abbas H. K. Al; Tran, Vu; Teeuwen, Ruben S. Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-60337-3	journal	February 2020
The nucleophilic amino group of lysine is central for histone lysine methyltransferase catalysis Al Temimi, Abbas H. K.; Amatdjais-Groenen, Helene I. V.; Reddy, Y. Vijayendar Communications Chemistry, Vol. 2, Issue 1 https://doi.org/10.1038/s42004-019-0210-8	journal	September 2019
Recognition of shorter and longer trimethyllysine analogues by epigenetic reader proteins Al Temimi, Abbas H. K.; Belle, Roman; Kumar, Kiran Chemical Communications, Vol. 54, Issue 19 https://doi.org/10.1039/c8cc01009a	journal	January 2018
Importance of the main chain of lysine for histone lysine methyltransferase catalysis Al Temimi, Abbas H. K.; Teeuwen, Ruben S.; Tran, Vu Organic & Biomolecular Chemistry, Vol. 17, Issue 23 https://doi.org/10.1039/c9ob01038f	journal	January 2019
Lysine Ethylation by Histone Lysine Methyltransferases Al Temimi, Abbas H. K.; Martin, Michael; Meng, Qingxi RWTH Aachen University https://doi.org/10.18154/rwth-2020-02217	text	January 2020

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