Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids

Detalhes bibliográficos
Autor(a) principal: Eberle, Raphael J. [UNESP]
Data de Publicação: 2018
Outros Autores: Kawai, Liege A. [UNESP], de Moraes, Fabio R. [UNESP], Olivier, Danilo [UNESP], do Amaral, Marcos S., Tasic, Ljubica, Arni, Raghuvir K. [UNESP], Coronado, Monika A. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.ijbiomac.2018.06.022
http://hdl.handle.net/11449/176424
Resumo: In pathogens, the thioredoxin system forms part of the defense against oxidative stress and ensures the formation of the proper disulfide bonds to ensure protein function. In Corynebacterium pseudotuberculosis, the role and mechanism of TrxA1 has not been elucidated, but, the significant homology among different Trxs and the conservation of the residues that form their active sites underline the importance of the Trx systems. Proteins involved in redox metabolism and low molecular weight thiols, which might interact with them, become attractive targets to modulate the activity of pathogens. The activity of the protein was investigated using a turbidimetric assay system. The influence of different pH and low molecular weight thiols were tested. Additionally, this assay was used to investigate the inhibitory potential of ligands from different molecular families, such as, polyanions (suramin and heparin) and flavonoids (hesperetin and hesperidin). All four compounds showed inhibition of the protein activity by approximately 80%. The interactions between these compounds and Cp-TrxA1 were investigated using CD spectroscopy, NMR, molecular docking and dynamics. Our results demonstrate that suramin and hesperetin can serve as lead molecules for the development of specific inhibitors for the C. pseudotuberculosis TrxA1.
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spelling Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoidsCorynebacterium pseudotuberculosisInhibitorMolecular dynamicsNMRThioredoxinIn pathogens, the thioredoxin system forms part of the defense against oxidative stress and ensures the formation of the proper disulfide bonds to ensure protein function. In Corynebacterium pseudotuberculosis, the role and mechanism of TrxA1 has not been elucidated, but, the significant homology among different Trxs and the conservation of the residues that form their active sites underline the importance of the Trx systems. Proteins involved in redox metabolism and low molecular weight thiols, which might interact with them, become attractive targets to modulate the activity of pathogens. The activity of the protein was investigated using a turbidimetric assay system. The influence of different pH and low molecular weight thiols were tested. Additionally, this assay was used to investigate the inhibitory potential of ligands from different molecular families, such as, polyanions (suramin and heparin) and flavonoids (hesperetin and hesperidin). All four compounds showed inhibition of the protein activity by approximately 80%. The interactions between these compounds and Cp-TrxA1 were investigated using CD spectroscopy, NMR, molecular docking and dynamics. Our results demonstrate that suramin and hesperetin can serve as lead molecules for the development of specific inhibitors for the C. pseudotuberculosis TrxA1.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do SulMultiuser Center for Biomolecular Innovation Department of Physics Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)Institute of Physics Federal University of Mato Grosso do SulChemical Biology Laboratory Organic Chemistry Department Institute of Chemistry University of Campinas (UNICAMP)Multiuser Center for Biomolecular Innovation Department of Physics Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)CNPq: 150444/2017-6FAPESP: 2009/53989-4FAPESP: 2015/13765-0FAPESP: 2015/18868-2FAPESP: 2016/08104-8FAPESP: 2016/12904-0Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul: 23/200.307/2014CNPq: 307338/2014-2CNPq: 401270/2014-9CNPq: 435913/2016-6Universidade Estadual Paulista (Unesp)Federal University of Mato Grosso do SulUniversidade Estadual de Campinas (UNICAMP)Eberle, Raphael J. [UNESP]Kawai, Liege A. [UNESP]de Moraes, Fabio R. [UNESP]Olivier, Danilo [UNESP]do Amaral, Marcos S.Tasic, LjubicaArni, Raghuvir K. [UNESP]Coronado, Monika A. [UNESP]2018-12-11T17:20:45Z2018-12-11T17:20:45Z2018-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1066-1073application/pdfhttp://dx.doi.org/10.1016/j.ijbiomac.2018.06.022International Journal of Biological Macromolecules, v. 117, p. 1066-1073.1879-00030141-8130http://hdl.handle.net/11449/17642410.1016/j.ijbiomac.2018.06.0222-s2.0-850482726842-s2.0-85048272684.pdf91625089789458870000-0003-2460-1145Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Biological Macromolecules0,917info:eu-repo/semantics/openAccess2023-11-01T06:14:35Zoai:repositorio.unesp.br:11449/176424Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:39:38.940744Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
title Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
spellingShingle Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
Eberle, Raphael J. [UNESP]
Corynebacterium pseudotuberculosis
Inhibitor
Molecular dynamics
NMR
Thioredoxin
title_short Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
title_full Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
title_fullStr Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
title_full_unstemmed Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
title_sort Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids
author Eberle, Raphael J. [UNESP]
author_facet Eberle, Raphael J. [UNESP]
Kawai, Liege A. [UNESP]
de Moraes, Fabio R. [UNESP]
Olivier, Danilo [UNESP]
do Amaral, Marcos S.
Tasic, Ljubica
Arni, Raghuvir K. [UNESP]
Coronado, Monika A. [UNESP]
author_role author
author2 Kawai, Liege A. [UNESP]
de Moraes, Fabio R. [UNESP]
Olivier, Danilo [UNESP]
do Amaral, Marcos S.
Tasic, Ljubica
Arni, Raghuvir K. [UNESP]
Coronado, Monika A. [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Federal University of Mato Grosso do Sul
Universidade Estadual de Campinas (UNICAMP)
dc.contributor.author.fl_str_mv Eberle, Raphael J. [UNESP]
Kawai, Liege A. [UNESP]
de Moraes, Fabio R. [UNESP]
Olivier, Danilo [UNESP]
do Amaral, Marcos S.
Tasic, Ljubica
Arni, Raghuvir K. [UNESP]
Coronado, Monika A. [UNESP]
dc.subject.por.fl_str_mv Corynebacterium pseudotuberculosis
Inhibitor
Molecular dynamics
NMR
Thioredoxin
topic Corynebacterium pseudotuberculosis
Inhibitor
Molecular dynamics
NMR
Thioredoxin
description In pathogens, the thioredoxin system forms part of the defense against oxidative stress and ensures the formation of the proper disulfide bonds to ensure protein function. In Corynebacterium pseudotuberculosis, the role and mechanism of TrxA1 has not been elucidated, but, the significant homology among different Trxs and the conservation of the residues that form their active sites underline the importance of the Trx systems. Proteins involved in redox metabolism and low molecular weight thiols, which might interact with them, become attractive targets to modulate the activity of pathogens. The activity of the protein was investigated using a turbidimetric assay system. The influence of different pH and low molecular weight thiols were tested. Additionally, this assay was used to investigate the inhibitory potential of ligands from different molecular families, such as, polyanions (suramin and heparin) and flavonoids (hesperetin and hesperidin). All four compounds showed inhibition of the protein activity by approximately 80%. The interactions between these compounds and Cp-TrxA1 were investigated using CD spectroscopy, NMR, molecular docking and dynamics. Our results demonstrate that suramin and hesperetin can serve as lead molecules for the development of specific inhibitors for the C. pseudotuberculosis TrxA1.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-11T17:20:45Z
2018-12-11T17:20:45Z
2018-10-01
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.2018.06.022
International Journal of Biological Macromolecules, v. 117, p. 1066-1073.
1879-0003
0141-8130
http://hdl.handle.net/11449/176424
10.1016/j.ijbiomac.2018.06.022
2-s2.0-85048272684
2-s2.0-85048272684.pdf
9162508978945887
0000-0003-2460-1145
url http://dx.doi.org/10.1016/j.ijbiomac.2018.06.022
http://hdl.handle.net/11449/176424
identifier_str_mv International Journal of Biological Macromolecules, v. 117, p. 1066-1073.
1879-0003
0141-8130
10.1016/j.ijbiomac.2018.06.022
2-s2.0-85048272684
2-s2.0-85048272684.pdf
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
0,917
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1066-1073
application/pdf
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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