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Crystal structure of trioxacarcin A covalently bound to DNA

We report a crystal structure that shows an antibiotic that extracts a nucleobase from a DNA molecule ‘caught in the act’ after forming a covalent bond but before departing with the base. The structure of trioxacarcin A covalently bound to double-stranded d(AACCGGTT) was determined to 1.78 Å resolut...

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Autores principales: Pfoh, Roland, Laatsch, Hartmut, Sheldrick, George M.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425490/
https://www.ncbi.nlm.nih.gov/pubmed/18453630
http://dx.doi.org/10.1093/nar/gkn245
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author Pfoh, Roland
Laatsch, Hartmut
Sheldrick, George M.
author_facet Pfoh, Roland
Laatsch, Hartmut
Sheldrick, George M.
author_sort Pfoh, Roland
collection PubMed
description We report a crystal structure that shows an antibiotic that extracts a nucleobase from a DNA molecule ‘caught in the act’ after forming a covalent bond but before departing with the base. The structure of trioxacarcin A covalently bound to double-stranded d(AACCGGTT) was determined to 1.78 Å resolution by MAD phasing employing brominated oligonucleotides. The DNA–drug complex has a unique structure that combines alkylation (at the N7 position of a guanine), intercalation (on the 3′-side of the alkylated guanine), and base flip-out. An antibiotic-induced flipping-out of a single, nonterminal nucleobase from a DNA duplex was observed for the first time in a crystal structure.
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spelling pubmed-24254902008-06-12 Crystal structure of trioxacarcin A covalently bound to DNA Pfoh, Roland Laatsch, Hartmut Sheldrick, George M. Nucleic Acids Res Structural Biology We report a crystal structure that shows an antibiotic that extracts a nucleobase from a DNA molecule ‘caught in the act’ after forming a covalent bond but before departing with the base. The structure of trioxacarcin A covalently bound to double-stranded d(AACCGGTT) was determined to 1.78 Å resolution by MAD phasing employing brominated oligonucleotides. The DNA–drug complex has a unique structure that combines alkylation (at the N7 position of a guanine), intercalation (on the 3′-side of the alkylated guanine), and base flip-out. An antibiotic-induced flipping-out of a single, nonterminal nucleobase from a DNA duplex was observed for the first time in a crystal structure. Oxford University Press 2008-06 2008-05-03 /pmc/articles/PMC2425490/ /pubmed/18453630 http://dx.doi.org/10.1093/nar/gkn245 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Pfoh, Roland
Laatsch, Hartmut
Sheldrick, George M.
Crystal structure of trioxacarcin A covalently bound to DNA
title Crystal structure of trioxacarcin A covalently bound to DNA
title_full Crystal structure of trioxacarcin A covalently bound to DNA
title_fullStr Crystal structure of trioxacarcin A covalently bound to DNA
title_full_unstemmed Crystal structure of trioxacarcin A covalently bound to DNA
title_short Crystal structure of trioxacarcin A covalently bound to DNA
title_sort crystal structure of trioxacarcin a covalently bound to dna
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425490/
https://www.ncbi.nlm.nih.gov/pubmed/18453630
http://dx.doi.org/10.1093/nar/gkn245
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