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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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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2008
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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. |
format | Text |
id | pubmed-2425490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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