| Autor: |
Hintzen JCJ; Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark., Poater J; ICREA and Departament de Química Inorgànica i Orgànica & IQTCUB, Universitat de Barcelona, Martí I Franquès 1-11, 08028 Barcelona, Spain., Kumar K; Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Al Temimi AHK; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6522 AJ Nijmegen, The Netherlands., Pieters BJGE; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6522 AJ Nijmegen, The Netherlands., Paton RS; Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Bickelhaupt FM; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6522 AJ Nijmegen, The Netherlands.; Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081HV Amsterdam, The Netherlands., Mecinović J; Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6522 AJ Nijmegen, The Netherlands. |
| Abstrakt: |
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. |
