Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes

Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (so-called holes) on purine nucleobases. The interaction of DNA with proteins may protect DNA from oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acids. Howev...

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Autores: Corbella Morató, Marina, Voityuk, Alexander A., Curutchet Barat, Carles E.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/175944
Acceso en línea:https://hdl.handle.net/2445/175944
Access Level:acceso abierto
Palabra clave:Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
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spelling Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI ComplexesCorbella Morató, MarinaVoityuk, Alexander A.Curutchet Barat, Carles E.Transferència d'energiaTransferència de càrregaADNReparació de l'ADNComplexitat computacionalEnergy transferCharge transferDNADNA repairComputational complexityDifferent mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (so-called holes) on purine nucleobases. The interaction of DNA with proteins may protect DNA from oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acids. However, how protein binding affects HT dynamics in DNA is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase HhaI with the aim of elucidating the molecular factors that explain why long-range DNA HT is inhibited when the glutamine residue inserted in the double helix is mutated into a tryptophan. We combine molecular dynamics, quantum chemistry, and kinetic Monte Carlo simulations and find that protein binding stabilizes the energies of the guanine radical cation states and significantly impacts the corresponding electronic couplings, thus determining the observed behavior, whereas the formation of a tryptophan radical leads to less efficient HT.American Chemical Society2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/175944Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1021/acs.jpclett.5b01683Journal of Physical Chemistry Letters, 2015, vol. 6, num. 18, p. 3749-3753https://doi.org/10.1021/acs.jpclett.5b01683(c) American Chemical Society , 2015info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1759442026-05-27T06:46:51Z
dc.title.none.fl_str_mv Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
title Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
spellingShingle Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
Corbella Morató, Marina
Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
title_short Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
title_full Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
title_fullStr Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
title_full_unstemmed Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
title_sort Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes
dc.creator.none.fl_str_mv Corbella Morató, Marina
Voityuk, Alexander A.
Curutchet Barat, Carles E.
author Corbella Morató, Marina
author_facet Corbella Morató, Marina
Voityuk, Alexander A.
Curutchet Barat, Carles E.
author_role author
author2 Voityuk, Alexander A.
Curutchet Barat, Carles E.
author2_role author
author
dc.subject.none.fl_str_mv Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
topic Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
description Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (so-called holes) on purine nucleobases. The interaction of DNA with proteins may protect DNA from oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acids. However, how protein binding affects HT dynamics in DNA is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase HhaI with the aim of elucidating the molecular factors that explain why long-range DNA HT is inhibited when the glutamine residue inserted in the double helix is mutated into a tryptophan. We combine molecular dynamics, quantum chemistry, and kinetic Monte Carlo simulations and find that protein binding stabilizes the energies of the guanine radical cation states and significantly impacts the corresponding electronic couplings, thus determining the observed behavior, whereas the formation of a tryptophan radical leads to less efficient HT.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/175944
url https://hdl.handle.net/2445/175944
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1021/acs.jpclett.5b01683
Journal of Physical Chemistry Letters, 2015, vol. 6, num. 18, p. 3749-3753
https://doi.org/10.1021/acs.jpclett.5b01683
dc.rights.none.fl_str_mv (c) American Chemical Society , 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Chemical Society , 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
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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score 15,300719

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