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

Autor: 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecules, Vol 25, Iss 8, p 1918 (2020)
Druh dokumentu: article
ISSN: 25081918
1420-3049
62428446
DOI: 10.3390/molecules25081918
Popis: 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.
Databáze: Directory of Open Access Journals
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