The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis

Detalhes bibliográficos
Autor(a) principal: Eberle, Raphael J. [UNESP]
Data de Publicação: 2019
Outros Autores: Coronado, Monika A. [UNESP], Peinado, Rafaela S. [UNESP], de Moraes, Fabio R. [UNESP], Olivier, Danilo [UNESP], Dreyer, Thiago [UNESP], de Oliveira Lopes, Debora, da Luz, Brenda Silva Rosa, Azevedo, Vasco, Arni, Raghuvir K. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.ijbiomac.2018.12.067
http://hdl.handle.net/11449/188482
Resumo: Currently no effective treatment is available to combat infections caused by Corynebacterium pseudotuberculosis in livestock. Survival of this Gram-positive bacterium in rapidly-growing pathogens in hostile environments is strongly dependent on the existence of a robust DNA repair system to prevent DNA mutations and contribute to bacterial colonization and virulence. The adenine/guanine-specific DNA glycosylase (MutY) is evolutionarily conserved and has been well characterized due to its central role in the prevention of mutagenesis and DNA repair. The aim of this study was the characterization of the target protein interaction with free adenine, suramin, and heparin, as well as the binding competition characterization between the molecules. The dissociation constant for free adenine interaction with Corynebacterium pseudotuberculosis MutY (Cp-MutY) was determined, 86 ± 2.5 μM. NMR competition experiments demonstrated, that the polyanions heparin and suramin compete with adenine for the protein active site. The determined dissociation constant for the heparin/Cp-MutY interaction was 5.9 ± 1.0 μM and for suramin was 16 ± 1.5 μM. Docking of both polyanions with Cp-MutY revealed a possible mode of interaction and indicates that these molecules can interfere with the protein interaction with damaged DNA or prevent the binding of the adenine base in the enzyme active site.
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spelling The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosisAdenineCompetitionCorynebacterium pseudotuberculosisMutYPolyanionsCurrently no effective treatment is available to combat infections caused by Corynebacterium pseudotuberculosis in livestock. Survival of this Gram-positive bacterium in rapidly-growing pathogens in hostile environments is strongly dependent on the existence of a robust DNA repair system to prevent DNA mutations and contribute to bacterial colonization and virulence. The adenine/guanine-specific DNA glycosylase (MutY) is evolutionarily conserved and has been well characterized due to its central role in the prevention of mutagenesis and DNA repair. The aim of this study was the characterization of the target protein interaction with free adenine, suramin, and heparin, as well as the binding competition characterization between the molecules. The dissociation constant for free adenine interaction with Corynebacterium pseudotuberculosis MutY (Cp-MutY) was determined, 86 ± 2.5 μM. NMR competition experiments demonstrated, that the polyanions heparin and suramin compete with adenine for the protein active site. The determined dissociation constant for the heparin/Cp-MutY interaction was 5.9 ± 1.0 μM and for suramin was 16 ± 1.5 μM. Docking of both polyanions with Cp-MutY revealed a possible mode of interaction and indicates that these molecules can interfere with the protein interaction with damaged DNA or prevent the binding of the adenine base in the enzyme active site.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Multiuser Center for Biomolecular Innovation Department of Physics Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)Departamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista Júlio de Mesquita Filho -UNESPLaboratory of Molecular Biology Universidade Federal de São João Del-Rei (CCO), Av. Sebastião Gonçalves Coelho, 400Laboratório de Genética Celular e Molecular Instituto de Ciências Biológicas Universidade Federal de Minas Gerais, Av, Antônio Carlos, 6627 - Pampulha, CP 486, CEP 31Multiuser Center for Biomolecular Innovation Department of Physics Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)Departamento de Física e Biofísica Instituto de Biociências Universidade Estadual Paulista Júlio de Mesquita Filho -UNESPFAPESP: 2009/53989-4FAPESP: 2015/13765-0FAPESP: 2015/18868-2FAPESP: 2016/08104-8FAPESP: 2016/12904-0CNPq: 307338/2014-2CNPq: 401270/2014-9CNPq: 435913/2016-6Universidade Estadual Paulista (Unesp)Universidade Federal de São João Del-Rei (CCO)Universidade Federal de Minas Gerais (UFMG)Eberle, Raphael J. [UNESP]Coronado, Monika A. [UNESP]Peinado, Rafaela S. [UNESP]de Moraes, Fabio R. [UNESP]Olivier, Danilo [UNESP]Dreyer, Thiago [UNESP]de Oliveira Lopes, Deborada Luz, Brenda Silva RosaAzevedo, VascoArni, Raghuvir K. [UNESP]2019-10-06T16:09:35Z2019-10-06T16:09:35Z2019-03-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article459-468http://dx.doi.org/10.1016/j.ijbiomac.2018.12.067International Journal of Biological Macromolecules, v. 125, p. 459-468.1879-00030141-8130http://hdl.handle.net/11449/18848210.1016/j.ijbiomac.2018.12.0672-s2.0-8505821849991625089789458870000-0003-2460-1145Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Biological Macromoleculesinfo:eu-repo/semantics/openAccess2021-10-23T05:55:20Zoai:repositorio.unesp.br:11449/188482Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:57:38.008606Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
title The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
spellingShingle The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
Eberle, Raphael J. [UNESP]
Adenine
Competition
Corynebacterium pseudotuberculosis
MutY
Polyanions
title_short The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
title_full The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
title_fullStr The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
title_full_unstemmed The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
title_sort The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis
author Eberle, Raphael J. [UNESP]
author_facet Eberle, Raphael J. [UNESP]
Coronado, Monika A. [UNESP]
Peinado, Rafaela S. [UNESP]
de Moraes, Fabio R. [UNESP]
Olivier, Danilo [UNESP]
Dreyer, Thiago [UNESP]
de Oliveira Lopes, Debora
da Luz, Brenda Silva Rosa
Azevedo, Vasco
Arni, Raghuvir K. [UNESP]
author_role author
author2 Coronado, Monika A. [UNESP]
Peinado, Rafaela S. [UNESP]
de Moraes, Fabio R. [UNESP]
Olivier, Danilo [UNESP]
Dreyer, Thiago [UNESP]
de Oliveira Lopes, Debora
da Luz, Brenda Silva Rosa
Azevedo, Vasco
Arni, Raghuvir K. [UNESP]
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade Federal de São João Del-Rei (CCO)
Universidade Federal de Minas Gerais (UFMG)
dc.contributor.author.fl_str_mv Eberle, Raphael J. [UNESP]
Coronado, Monika A. [UNESP]
Peinado, Rafaela S. [UNESP]
de Moraes, Fabio R. [UNESP]
Olivier, Danilo [UNESP]
Dreyer, Thiago [UNESP]
de Oliveira Lopes, Debora
da Luz, Brenda Silva Rosa
Azevedo, Vasco
Arni, Raghuvir K. [UNESP]
dc.subject.por.fl_str_mv Adenine
Competition
Corynebacterium pseudotuberculosis
MutY
Polyanions
topic Adenine
Competition
Corynebacterium pseudotuberculosis
MutY
Polyanions
description Currently no effective treatment is available to combat infections caused by Corynebacterium pseudotuberculosis in livestock. Survival of this Gram-positive bacterium in rapidly-growing pathogens in hostile environments is strongly dependent on the existence of a robust DNA repair system to prevent DNA mutations and contribute to bacterial colonization and virulence. The adenine/guanine-specific DNA glycosylase (MutY) is evolutionarily conserved and has been well characterized due to its central role in the prevention of mutagenesis and DNA repair. The aim of this study was the characterization of the target protein interaction with free adenine, suramin, and heparin, as well as the binding competition characterization between the molecules. The dissociation constant for free adenine interaction with Corynebacterium pseudotuberculosis MutY (Cp-MutY) was determined, 86 ± 2.5 μM. NMR competition experiments demonstrated, that the polyanions heparin and suramin compete with adenine for the protein active site. The determined dissociation constant for the heparin/Cp-MutY interaction was 5.9 ± 1.0 μM and for suramin was 16 ± 1.5 μM. Docking of both polyanions with Cp-MutY revealed a possible mode of interaction and indicates that these molecules can interfere with the protein interaction with damaged DNA or prevent the binding of the adenine base in the enzyme active site.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-06T16:09:35Z
2019-10-06T16:09:35Z
2019-03-15
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.ijbiomac.2018.12.067
International Journal of Biological Macromolecules, v. 125, p. 459-468.
1879-0003
0141-8130
http://hdl.handle.net/11449/188482
10.1016/j.ijbiomac.2018.12.067
2-s2.0-85058218499
9162508978945887
0000-0003-2460-1145
url http://dx.doi.org/10.1016/j.ijbiomac.2018.12.067
http://hdl.handle.net/11449/188482
identifier_str_mv International Journal of Biological Macromolecules, v. 125, p. 459-468.
1879-0003
0141-8130
10.1016/j.ijbiomac.2018.12.067
2-s2.0-85058218499
9162508978945887
0000-0003-2460-1145
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv International Journal of Biological Macromolecules
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 459-468
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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