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

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

doi:10.3390/molecules25081918

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

Jordi C. J. Hintzen

^1,†

Jordi Poater

^2,†,

Kiran Kumar

^3,†,

Abbas H. K. Al Temimi

^4,†,

Bas J. G. E. Pieters

⁴,

Robert S. Paton

^3,*

F. Matthias Bickelhaupt

^4,5,*

and

Jasmin Mecinović

^1,4,*

Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark

ICREA and Departament de Química Inorgànica i Orgànica & IQTCUB, Universitat de Barcelona, Martí I Franquès 1–11, 08028 Barcelona, Spain

Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK

⁴

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6522 AJ Nijmegen, The Netherlands

⁵

Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081HV Amsterdam, The Netherlands

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editors: Ivo Piantanida and Adegboyega K. Oyelere

Molecules 2020, 25(8), 1918; https://doi.org/10.3390/molecules25081918

Received: 26 February 2020 / Revised: 16 April 2020 / Accepted: 16 April 2020 / Published: 21 April 2020

(This article belongs to the Special Issue Exclusive Papers of the Editorial Board Members (EBMs) of the Bioorganic Chemistry Section of Molecules)

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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. View Full-Text

Keywords: epigenetics; histone; lysine methylation; molecular recognition; noncovalent interactions

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MDPI and ACS Style

Hintzen, J.C.J.; Poater, J.; Kumar, K.; Al Temimi, A.H.K.; Pieters, B.J.G.E.; Paton, R.S.; Bickelhaupt, F.M.; Mecinović, J. Comparison of Molecular Recognition of Trimethyllysine and Trimethylthialysine by Epigenetic Reader Proteins. Molecules 2020, 25, 1918. https://doi.org/10.3390/molecules25081918

AMA Style

Hintzen JCJ, Poater J, Kumar K, Al Temimi AHK, Pieters BJGE, Paton RS, Bickelhaupt FM, Mecinović J. Comparison of Molecular Recognition of Trimethyllysine and Trimethylthialysine by Epigenetic Reader Proteins. Molecules. 2020; 25(8):1918. https://doi.org/10.3390/molecules25081918

Chicago/Turabian Style

Hintzen, Jordi C.J., Jordi Poater, Kiran Kumar, Abbas H.K. Al Temimi, Bas J.G.E. Pieters, Robert S. Paton, F. M. Bickelhaupt, and Jasmin Mecinović. 2020. "Comparison of Molecular Recognition of Trimethyllysine and Trimethylthialysine by Epigenetic Reader Proteins" Molecules 25, no. 8: 1918. https://doi.org/10.3390/molecules25081918

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

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