Comparison of Molecular Recognition of Trimethyllysine and Trimethylthialysine by Epigenetic Reader Proteins

Jordi C J Hintzen, Jordi Poater, Kiran Kumar, Abbas H K Al Temimi, Bas J G E Pieters, Robert S Paton*, F Matthias Bickelhaupt*, Jasmin Mecinović

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Gaining a fundamental insight into the biomolecular recognition of posttranslationally modified histones by epigenetic reader proteins is of crucial importance to understanding the regulation of the activity of human genes. Here, we seek to establish whether trimethylthialysine, a simple trimethyllysine analogue generated through cysteine alkylation, is a good trimethyllysine mimic for studies on molecular recognition by reader proteins. Histone peptides bearing trimethylthialysine and trimethyllysine were examined for binding with five human reader proteins employing a combination of thermodynamic analyses, molecular dynamics simulations and quantum chemical analyses. Collectively, our experimental and computational findings reveal that trimethylthialysine and trimethyllysine exhibit very similar binding characteristics for the association with human reader proteins, thereby justifying the use of trimethylthialysine for studies aimed at dissecting the origin of biomolecular recognition in epigenetic processes that play important roles in human health and disease.

Original languageEnglish
Article number1918
JournalMolecules
Volume25
Issue number8
Number of pages14
ISSN1420-3049
DOIs
Publication statusPublished - Apr 2020

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