Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger

The understanding of biomolecular recognition of posttranslationally modified histone proteins is centrally important to the histone code hypothesis. Despite extensive binding and structural studies on the readout of histones, the molecular language by which posttranslational modifications on histon...

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Autores: Pieters, Bas J. G. E., Wuts, Maud H. M., Poater i Teixidor, Jordi, Kumar, Kiran, White, Paul B., Kamps, Jos J. A. G., Sherman, Woody, Pruijn, Ger J. M., Paton, Robert S., Beumimg, Thijs, Bickelhaupt, F. Matthias, Mecinović, Jasmin
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/196125
Acceso en línea:https://hdl.handle.net/2445/196125
Access Level:acceso abierto
Palabra clave:Reconeixement molecular
Histones
Metilació
Molecular recognition
Methylation
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spelling Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 fingerPieters, Bas J. G. E.Wuts, Maud H. M.Poater i Teixidor, JordiKumar, KiranWhite, Paul B.Kamps, Jos J. A. G.Sherman, WoodyPruijn, Ger J. M.Paton, Robert S.Beumimg, ThijsBickelhaupt, F. MatthiasMecinović, JasminReconeixement molecularHistonesMetilacióMolecular recognitionHistonesMethylationThe understanding of biomolecular recognition of posttranslationally modified histone proteins is centrally important to the histone code hypothesis. Despite extensive binding and structural studies on the readout of histones, the molecular language by which posttranslational modifications on histone proteins are read remains poorly understood. Here we report physical-organic chemistry studies on the recognition of the positively charged trimethyllysine by the electron-rich aromatic cage containing PHD3 finger of KDM5A. The aromatic character of two tryptophan residues that solely constitute the aromatic cage of KDM5A was fine-tuned by the incorporation of fluorine substituents. Our thermodynamic analyses reveal that the wild-type and fluorinated KDM5A PHD3 fingers associate equally well with trimethyllysine. This work demonstrates that the biomolecular recognition of trimethyllysine by fluorinated aromatic cages is associated with weaker cation-π interactions that are compensated by the energetically more favourable trimethyllysine-mediated release of high-energy water molecules that occupy the aromatic cage.Springer Nature2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/196125Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s42004-020-0313-2Communications Chemistry, 2020, vol. 3, p. 69https://doi.org/10.1038/s42004-020-0313-2cc-by (c) Pieters, Bas J. G. E. et al., 2020https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1961252026-05-27T06:46:51Z
dc.title.none.fl_str_mv Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
title Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
spellingShingle Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
Pieters, Bas J. G. E.
Reconeixement molecular
Histones
Metilació
Molecular recognition
Histones
Methylation
title_short Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
title_full Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
title_fullStr Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
title_full_unstemmed Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
title_sort Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger
dc.creator.none.fl_str_mv Pieters, Bas J. G. E.
Wuts, Maud H. M.
Poater i Teixidor, Jordi
Kumar, Kiran
White, Paul B.
Kamps, Jos J. A. G.
Sherman, Woody
Pruijn, Ger J. M.
Paton, Robert S.
Beumimg, Thijs
Bickelhaupt, F. Matthias
Mecinović, Jasmin
author Pieters, Bas J. G. E.
author_facet Pieters, Bas J. G. E.
Wuts, Maud H. M.
Poater i Teixidor, Jordi
Kumar, Kiran
White, Paul B.
Kamps, Jos J. A. G.
Sherman, Woody
Pruijn, Ger J. M.
Paton, Robert S.
Beumimg, Thijs
Bickelhaupt, F. Matthias
Mecinović, Jasmin
author_role author
author2 Wuts, Maud H. M.
Poater i Teixidor, Jordi
Kumar, Kiran
White, Paul B.
Kamps, Jos J. A. G.
Sherman, Woody
Pruijn, Ger J. M.
Paton, Robert S.
Beumimg, Thijs
Bickelhaupt, F. Matthias
Mecinović, Jasmin
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Reconeixement molecular
Histones
Metilació
Molecular recognition
Histones
Methylation
topic Reconeixement molecular
Histones
Metilació
Molecular recognition
Histones
Methylation
description The understanding of biomolecular recognition of posttranslationally modified histone proteins is centrally important to the histone code hypothesis. Despite extensive binding and structural studies on the readout of histones, the molecular language by which posttranslational modifications on histone proteins are read remains poorly understood. Here we report physical-organic chemistry studies on the recognition of the positively charged trimethyllysine by the electron-rich aromatic cage containing PHD3 finger of KDM5A. The aromatic character of two tryptophan residues that solely constitute the aromatic cage of KDM5A was fine-tuned by the incorporation of fluorine substituents. Our thermodynamic analyses reveal that the wild-type and fluorinated KDM5A PHD3 fingers associate equally well with trimethyllysine. This work demonstrates that the biomolecular recognition of trimethyllysine by fluorinated aromatic cages is associated with weaker cation-π interactions that are compensated by the energetically more favourable trimethyllysine-mediated release of high-energy water molecules that occupy the aromatic cage.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/196125
url https://hdl.handle.net/2445/196125
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s42004-020-0313-2
Communications Chemistry, 2020, vol. 3, p. 69
https://doi.org/10.1038/s42004-020-0313-2
dc.rights.none.fl_str_mv cc-by (c) Pieters, Bas J. G. E. et al., 2020
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Pieters, Bas J. G. E. et al., 2020
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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