Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication

Detalhes bibliográficos
Autor(a) principal: Soares, Flávia V.
Data de Publicação: 2018
Outros Autores: Castro, Alexandre A. de, Pereira, Ander F., Leal, Daniel H. S., Mancini, Daiana T., Krejcar, Ondrej, Ramalho, Teodorico C., Cunha, Elaine F. F. da, Kuca, Kamil
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFLA
Texto Completo: http://repositorio.ufla.br/jspui/handle/1/33371
Resumo: Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.
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spelling Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxicationOrganophosphorus compoundsDiisopropyl fluorophosphataseCyclosarinMolecular dockingPrincipal components analysisCompostos organofosforadosFluorofosfatase de diisopropiloCiclosarinaDocagem molecularAnálise de componentes principaisOrganophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.MDPI2019-04-01T11:33:14Z2019-04-01T11:33:14Z2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfSOARES, F. V. et al. Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication. International Journal of Molecular Sciences, [S. l.], v. 19, n. 4, p. 1-18, 2018. DOI: https://doi.org/10.3390/ijms19041257.http://repositorio.ufla.br/jspui/handle/1/33371International Journal of Molecular Sciencesreponame:Repositório Institucional da UFLAinstname:Universidade Federal de Lavras (UFLA)instacron:UFLAhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessSoares, Flávia V.Castro, Alexandre A. dePereira, Ander F.Leal, Daniel H. S.Mancini, Daiana T.Krejcar, OndrejRamalho, Teodorico C.Cunha, Elaine F. F. daKuca, Kamileng2019-04-01T11:33:14Zoai:localhost:1/33371Repositório InstitucionalPUBhttp://repositorio.ufla.br/oai/requestnivaldo@ufla.br || repositorio.biblioteca@ufla.bropendoar:2019-04-01T11:33:14Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA)false
dc.title.none.fl_str_mv Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
title Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
spellingShingle Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
Soares, Flávia V.
Organophosphorus compounds
Diisopropyl fluorophosphatase
Cyclosarin
Molecular docking
Principal components analysis
Compostos organofosforados
Fluorofosfatase de diisopropilo
Ciclosarina
Docagem molecular
Análise de componentes principais
title_short Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
title_full Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
title_fullStr Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
title_full_unstemmed Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
title_sort Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication
author Soares, Flávia V.
author_facet Soares, Flávia V.
Castro, Alexandre A. de
Pereira, Ander F.
Leal, Daniel H. S.
Mancini, Daiana T.
Krejcar, Ondrej
Ramalho, Teodorico C.
Cunha, Elaine F. F. da
Kuca, Kamil
author_role author
author2 Castro, Alexandre A. de
Pereira, Ander F.
Leal, Daniel H. S.
Mancini, Daiana T.
Krejcar, Ondrej
Ramalho, Teodorico C.
Cunha, Elaine F. F. da
Kuca, Kamil
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Soares, Flávia V.
Castro, Alexandre A. de
Pereira, Ander F.
Leal, Daniel H. S.
Mancini, Daiana T.
Krejcar, Ondrej
Ramalho, Teodorico C.
Cunha, Elaine F. F. da
Kuca, Kamil
dc.subject.por.fl_str_mv Organophosphorus compounds
Diisopropyl fluorophosphatase
Cyclosarin
Molecular docking
Principal components analysis
Compostos organofosforados
Fluorofosfatase de diisopropilo
Ciclosarina
Docagem molecular
Análise de componentes principais
topic Organophosphorus compounds
Diisopropyl fluorophosphatase
Cyclosarin
Molecular docking
Principal components analysis
Compostos organofosforados
Fluorofosfatase de diisopropilo
Ciclosarina
Docagem molecular
Análise de componentes principais
description Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019-04-01T11:33:14Z
2019-04-01T11:33:14Z
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 SOARES, F. V. et al. Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication. International Journal of Molecular Sciences, [S. l.], v. 19, n. 4, p. 1-18, 2018. DOI: https://doi.org/10.3390/ijms19041257.
http://repositorio.ufla.br/jspui/handle/1/33371
identifier_str_mv SOARES, F. V. et al. Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication. International Journal of Molecular Sciences, [S. l.], v. 19, n. 4, p. 1-18, 2018. DOI: https://doi.org/10.3390/ijms19041257.
url http://repositorio.ufla.br/jspui/handle/1/33371
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv International Journal of Molecular Sciences
reponame:Repositório Institucional da UFLA
instname:Universidade Federal de Lavras (UFLA)
instacron:UFLA
instname_str Universidade Federal de Lavras (UFLA)
instacron_str UFLA
institution UFLA
reponame_str Repositório Institucional da UFLA
collection Repositório Institucional da UFLA
repository.name.fl_str_mv Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA)
repository.mail.fl_str_mv nivaldo@ufla.br || repositorio.biblioteca@ufla.br
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