Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.

Alkylpurine glycosylase D (AlkD) exhibits a unique base excision strategy. Instead of interacting directly with the lesion, the enzyme engages the non-lesion DNA strand. AlkD induces flipping of the alkylated and opposing base accompanied by DNA stack compression. Since this strategy leaves the alky...

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Autores principales:	Bradley Kossmann, Ivaylo Ivanov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/63e64a743f234f9f95bdb27d42c54029
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spelling	oai:doaj.org-article:63e64a743f234f9f95bdb27d42c540292021-11-25T05:41:00ZAlkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.1553-734X1553-735810.1371/journal.pcbi.1003704https://doaj.org/article/63e64a743f234f9f95bdb27d42c540292014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24992034/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Alkylpurine glycosylase D (AlkD) exhibits a unique base excision strategy. Instead of interacting directly with the lesion, the enzyme engages the non-lesion DNA strand. AlkD induces flipping of the alkylated and opposing base accompanied by DNA stack compression. Since this strategy leaves the alkylated base solvent exposed, the means to achieve enzymatic cleavage had remained unclear. We determined a minimum energy path for flipping out a 3-methyl adenine by AlkD and computed a potential of mean force along this path to delineate the energetics of base extrusion. We show that AlkD acts as a scaffold to stabilize three distinct DNA conformations, including the final extruded state. These states are almost equivalent in free energy and separated by low barriers. Thus, AlkD acts by sculpting the global DNA conformation to achieve lesion expulsion from DNA. N-glycosidic bond scission is then facilitated by a backbone phosphate group proximal to the alkylated base.Bradley KossmannIvaylo IvanovPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 7, p e1003704 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Bradley Kossmann Ivaylo Ivanov Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.
description	Alkylpurine glycosylase D (AlkD) exhibits a unique base excision strategy. Instead of interacting directly with the lesion, the enzyme engages the non-lesion DNA strand. AlkD induces flipping of the alkylated and opposing base accompanied by DNA stack compression. Since this strategy leaves the alkylated base solvent exposed, the means to achieve enzymatic cleavage had remained unclear. We determined a minimum energy path for flipping out a 3-methyl adenine by AlkD and computed a potential of mean force along this path to delineate the energetics of base extrusion. We show that AlkD acts as a scaffold to stabilize three distinct DNA conformations, including the final extruded state. These states are almost equivalent in free energy and separated by low barriers. Thus, AlkD acts by sculpting the global DNA conformation to achieve lesion expulsion from DNA. N-glycosidic bond scission is then facilitated by a backbone phosphate group proximal to the alkylated base.
format	article
author	Bradley Kossmann Ivaylo Ivanov
author_facet	Bradley Kossmann Ivaylo Ivanov
author_sort	Bradley Kossmann
title	Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.
title_short	Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.
title_full	Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.
title_fullStr	Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.
title_full_unstemmed	Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.
title_sort	alkylpurine glycosylase d employs dna sculpting as a strategy to extrude and excise damaged bases.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/63e64a743f234f9f95bdb27d42c54029
work_keys_str_mv	AT bradleykossmann alkylpurineglycosylasedemploysdnasculptingasastrategytoextrudeandexcisedamagedbases AT ivayloivanov alkylpurineglycosylasedemploysdnasculptingasastrategytoextrudeandexcisedamagedbases
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Alkylpurine glycosylase D employs DNA sculpting as a strategy to extrude and excise damaged bases.

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