1. Exploring the Histone Acylome through Incorporation of γ-Thialysine on Histone Tails
- Author
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Jordi C. J. Hintzen, Giorgio Rainone, Jasmin Mecinović, and Giordano Proietti
- Subjects
Models, Molecular ,Lysine Acetyltransferases ,Protein Conformation ,Acylation ,Lysine ,Biomedical Engineering ,Pharmaceutical Science ,Bioengineering ,02 engineering and technology ,complex mixtures ,01 natural sciences ,Histones ,chemistry.chemical_compound ,Non-histone protein ,Histone tails ,Humans ,Cysteine ,Histone Acetyltransferases ,Pharmacology ,Thialysine ,biology ,010405 organic chemistry ,Organic Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,3. Good health ,Kinetics ,Histone ,Biochemistry ,chemistry ,Biocatalysis ,biology.protein ,bacteria ,Acetyl coenzyme ,0210 nano-technology ,Biotechnology - Abstract
Histone lysine acetyltransferases (KATs) catalyze the transfer of the acetyl group from acetyl Coenzyme A to lysine residues in histones and nonhistone proteins. Here, we report biomolecular studies on epigenetic acetylation and related acylation reactions of lysine and γ-thialysine, a cysteine-derived lysine mimic, which can be site-specifically introduced to histone peptides and histone proteins. Enzyme assays demonstrate that human KATs catalyze an efficient acetylation and propionylation of histone peptides that possess lysine and γ-thialysine. Enzyme kinetics analyses reveal that lysine- and γ-thialysine-containing histone peptides exhibit indistinguishable Km values, whereas small differences in kcat values were observed. This work highlights that γ-thialysine may act as a representative and easily accessible lysine mimic for chemical and biochemical examinations of post-translationally modified histones.
- Published
- 2020
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