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Modulation of Hoogsteen dynamics on DNA recognition

In naked duplex DNA, G–C and A–T Watson-Crick base pairs exist in dynamic equilibrium with their Hoogsteen counterparts. Here, we used nuclear magnetic resonance (NMR) relaxation dispersion and molecular dynamics (MD) simulations to examine how Watson-Crick/Hoogsteen dynamics are modulated upon reco...

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Autores principales: Xu, Yu, McSally, James, Andricioaei, Ioan, Al-Hashimi, Hashim M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902632/
https://www.ncbi.nlm.nih.gov/pubmed/29662229
http://dx.doi.org/10.1038/s41467-018-03516-1
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author Xu, Yu
McSally, James
Andricioaei, Ioan
Al-Hashimi, Hashim M.
author_facet Xu, Yu
McSally, James
Andricioaei, Ioan
Al-Hashimi, Hashim M.
author_sort Xu, Yu
collection PubMed
description In naked duplex DNA, G–C and A–T Watson-Crick base pairs exist in dynamic equilibrium with their Hoogsteen counterparts. Here, we used nuclear magnetic resonance (NMR) relaxation dispersion and molecular dynamics (MD) simulations to examine how Watson-Crick/Hoogsteen dynamics are modulated upon recognition of duplex DNA by the bisintercalator echinomycin and monointercalator actinomycin D. In both cases, DNA recognition results in the quenching of Hoogsteen dynamics at base pairs involved in intermolecular base-specific hydrogen bonds. In the case of echinomycin, the Hoogsteen population increased 10-fold for base pairs flanking the chromophore most likely due to intermolecular stacking interactions, whereas actinomycin D minimally affected Hoogsteen dynamics at other sites. Modulation of Hoogsteen dynamics at binding interfaces may be a general phenomenon with important implications for DNA–ligand and DNA–protein recognition.
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spelling pubmed-59026322018-04-20 Modulation of Hoogsteen dynamics on DNA recognition Xu, Yu McSally, James Andricioaei, Ioan Al-Hashimi, Hashim M. Nat Commun Article In naked duplex DNA, G–C and A–T Watson-Crick base pairs exist in dynamic equilibrium with their Hoogsteen counterparts. Here, we used nuclear magnetic resonance (NMR) relaxation dispersion and molecular dynamics (MD) simulations to examine how Watson-Crick/Hoogsteen dynamics are modulated upon recognition of duplex DNA by the bisintercalator echinomycin and monointercalator actinomycin D. In both cases, DNA recognition results in the quenching of Hoogsteen dynamics at base pairs involved in intermolecular base-specific hydrogen bonds. In the case of echinomycin, the Hoogsteen population increased 10-fold for base pairs flanking the chromophore most likely due to intermolecular stacking interactions, whereas actinomycin D minimally affected Hoogsteen dynamics at other sites. Modulation of Hoogsteen dynamics at binding interfaces may be a general phenomenon with important implications for DNA–ligand and DNA–protein recognition. Nature Publishing Group UK 2018-04-16 /pmc/articles/PMC5902632/ /pubmed/29662229 http://dx.doi.org/10.1038/s41467-018-03516-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Xu, Yu
McSally, James
Andricioaei, Ioan
Al-Hashimi, Hashim M.
Modulation of Hoogsteen dynamics on DNA recognition
title Modulation of Hoogsteen dynamics on DNA recognition
title_full Modulation of Hoogsteen dynamics on DNA recognition
title_fullStr Modulation of Hoogsteen dynamics on DNA recognition
title_full_unstemmed Modulation of Hoogsteen dynamics on DNA recognition
title_short Modulation of Hoogsteen dynamics on DNA recognition
title_sort modulation of hoogsteen dynamics on dna recognition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902632/
https://www.ncbi.nlm.nih.gov/pubmed/29662229
http://dx.doi.org/10.1038/s41467-018-03516-1
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