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Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats
3-methyladenine DNA glycosylases initiate repair of cytotoxic and promutagenic alkylated bases in DNA. We demonstrate by comparative modelling that Bacillus cereus AlkD belongs to a new, fifth, structural superfamily of DNA glycosylases with an alpha–alpha superhelix fold comprising six HEAT-like re...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874660/ https://www.ncbi.nlm.nih.gov/pubmed/17395642 http://dx.doi.org/10.1093/nar/gkm039 |
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author | Dalhus, Bjørn Helle, Ina Høydal Backe, Paul H. Alseth, Ingrun Rognes, Torbjørn Bjørås, Magnar Laerdahl, Jon K. |
author_facet | Dalhus, Bjørn Helle, Ina Høydal Backe, Paul H. Alseth, Ingrun Rognes, Torbjørn Bjørås, Magnar Laerdahl, Jon K. |
author_sort | Dalhus, Bjørn |
collection | PubMed |
description | 3-methyladenine DNA glycosylases initiate repair of cytotoxic and promutagenic alkylated bases in DNA. We demonstrate by comparative modelling that Bacillus cereus AlkD belongs to a new, fifth, structural superfamily of DNA glycosylases with an alpha–alpha superhelix fold comprising six HEAT-like repeats. The structure reveals a wide, positively charged groove, including a putative base recognition pocket. This groove appears to be suitable for the accommodation of double-stranded DNA with a flipped-out alkylated base. Site-specific mutagenesis within the recognition pocket identified several residues essential for enzyme activity. The results suggest that the aromatic side chain of a tryptophan residue recognizes electron-deficient alkylated bases through stacking interactions, while an interacting aspartate–arginine pair is essential for removal of the damaged base. A structural model of AlkD bound to DNA with a flipped-out purine moiety gives insight into the catalytic machinery for this new class of DNA glycosylases. |
format | Text |
id | pubmed-1874660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-18746602007-05-25 Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats Dalhus, Bjørn Helle, Ina Høydal Backe, Paul H. Alseth, Ingrun Rognes, Torbjørn Bjørås, Magnar Laerdahl, Jon K. Nucleic Acids Res Structural Biology 3-methyladenine DNA glycosylases initiate repair of cytotoxic and promutagenic alkylated bases in DNA. We demonstrate by comparative modelling that Bacillus cereus AlkD belongs to a new, fifth, structural superfamily of DNA glycosylases with an alpha–alpha superhelix fold comprising six HEAT-like repeats. The structure reveals a wide, positively charged groove, including a putative base recognition pocket. This groove appears to be suitable for the accommodation of double-stranded DNA with a flipped-out alkylated base. Site-specific mutagenesis within the recognition pocket identified several residues essential for enzyme activity. The results suggest that the aromatic side chain of a tryptophan residue recognizes electron-deficient alkylated bases through stacking interactions, while an interacting aspartate–arginine pair is essential for removal of the damaged base. A structural model of AlkD bound to DNA with a flipped-out purine moiety gives insight into the catalytic machinery for this new class of DNA glycosylases. Oxford University Press 2007-04 2007-03-29 /pmc/articles/PMC1874660/ /pubmed/17395642 http://dx.doi.org/10.1093/nar/gkm039 Text en © 2007 The Author(s) 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 Dalhus, Bjørn Helle, Ina Høydal Backe, Paul H. Alseth, Ingrun Rognes, Torbjørn Bjørås, Magnar Laerdahl, Jon K. Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats |
title | Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats |
title_full | Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats |
title_fullStr | Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats |
title_full_unstemmed | Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats |
title_short | Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats |
title_sort | structural insight into repair of alkylated dna by a new superfamily of dna glycosylases comprising heat-like repeats |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874660/ https://www.ncbi.nlm.nih.gov/pubmed/17395642 http://dx.doi.org/10.1093/nar/gkm039 |
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