Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study

Detalhes bibliográficos
Autor(a) principal: Sanches, Karoline [UNESP]
Data de Publicação: 2019
Outros Autores: Dias, Raphael Vinicius Rodrigues [UNESP], da Silva, Paulo Henrique [UNESP], Fossey, Marcelo Andrés [UNESP], Caruso, Ícaro Putinhon [UNESP], de Souza, Fátima Pereira [UNESP], de Oliveira, Leandro Cristante [UNESP], de Melo, Fernando Alves [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.heliyon.2019.e02869
http://hdl.handle.net/11449/201350
Resumo: Grb2 is an important regulator of normal vs. oncogenic cell signaling transduction. It plays a pivotal role on kinase-mediated signaling transduction by linking Receptor Tyrosine kinases to Ras/MAPK pathway which is known to bring oncogenic outcome. Coumarins are phenolic molecules found in several plants and seeds widely studied because of the antibiotic, anti-inflammatory, anticoagulant, vasodilator, and anti-tumor properties. Despite several studies about the anti-tumor properties of Coumarin in vivo and the role of Grb2 in signaling pathways related to cell proliferation, a molecular level investigation of the interaction between Grb2 and Coumarin is still missing. In this study, we performed a combined set of biophysical approaches to get insights on the interaction between Grb2 in a dimer state and Coumarin. Our results showed that Coumarin interacts with Grb2 dimer through its SH2 domain. The interaction is entropically driven, 1:1 molecular ratio and presents equilibrium constant of 105 M−1. In fact, SH2 is a well-known domain and a versatile signaling module for drug targeting which has been reported to bind compounds that block Ras activation in vivo. Despite we don't know the biological role coming from interaction between Grb2-SH2 domain and Coumarin, it is clear that this molecule could work in the same way as a SH2 domain inhibitor in order to block the link of Receptor Tyrosine kinases to Ras/MAPK pathway.
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spelling Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling studyBiochemistryBiomoleculesBiophysical chemistryBiophysicsCoumarinFluorescenceGrb2Molecular biologyMolecular dockingMolecular dynamicsSpectroscopySTD-NMRGrb2 is an important regulator of normal vs. oncogenic cell signaling transduction. It plays a pivotal role on kinase-mediated signaling transduction by linking Receptor Tyrosine kinases to Ras/MAPK pathway which is known to bring oncogenic outcome. Coumarins are phenolic molecules found in several plants and seeds widely studied because of the antibiotic, anti-inflammatory, anticoagulant, vasodilator, and anti-tumor properties. Despite several studies about the anti-tumor properties of Coumarin in vivo and the role of Grb2 in signaling pathways related to cell proliferation, a molecular level investigation of the interaction between Grb2 and Coumarin is still missing. In this study, we performed a combined set of biophysical approaches to get insights on the interaction between Grb2 in a dimer state and Coumarin. Our results showed that Coumarin interacts with Grb2 dimer through its SH2 domain. The interaction is entropically driven, 1:1 molecular ratio and presents equilibrium constant of 105 M−1. In fact, SH2 is a well-known domain and a versatile signaling module for drug targeting which has been reported to bind compounds that block Ras activation in vivo. Despite we don't know the biological role coming from interaction between Grb2-SH2 domain and Coumarin, it is clear that this molecule could work in the same way as a SH2 domain inhibitor in order to block the link of Receptor Tyrosine kinases to Ras/MAPK pathway.Biochemistry; Molecular biology; Biophysics; Biophysical chemistry; Spectroscopy; Biomolecules; Molecular docking; Molecular dynamics; Grb2; Coumarin; Fluorescence; STD-NMR; Molecular dockingFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University “Júlio de Mesquita Filho” (UNESP)Multiuser Center for Biomolecular Innovation (CMIB) Institute of Biosciences Humanities and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP)Department of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University “Júlio de Mesquita Filho” (UNESP)Multiuser Center for Biomolecular Innovation (CMIB) Institute of Biosciences Humanities and Exact Sciences (IBILCE) São Paulo State University “Júlio de Mesquita Filho” (UNESP)FAPESP: 2009/53989-4FAPESP: 2014/17630-0FAPESP: 2016/08753-6CNPq: 442352/2014-0CNPq: 442951/2014-0Universidade Estadual Paulista (Unesp)Sanches, Karoline [UNESP]Dias, Raphael Vinicius Rodrigues [UNESP]da Silva, Paulo Henrique [UNESP]Fossey, Marcelo Andrés [UNESP]Caruso, Ícaro Putinhon [UNESP]de Souza, Fátima Pereira [UNESP]de Oliveira, Leandro Cristante [UNESP]de Melo, Fernando Alves [UNESP]2020-12-12T02:30:19Z2020-12-12T02:30:19Z2019-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.heliyon.2019.e02869Heliyon, v. 5, n. 11, 2019.2405-8440http://hdl.handle.net/11449/20135010.1016/j.heliyon.2019.e028692-s2.0-85075511597331351133478398697689884160427700000-0002-4731-49770000-0002-8676-3150Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengHeliyoninfo:eu-repo/semantics/openAccess2021-10-23T10:11:17Zoai:repositorio.unesp.br:11449/201350Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T13:49:31.290766Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
title Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
spellingShingle Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
Sanches, Karoline [UNESP]
Biochemistry
Biomolecules
Biophysical chemistry
Biophysics
Coumarin
Fluorescence
Grb2
Molecular biology
Molecular docking
Molecular dynamics
Spectroscopy
STD-NMR
title_short Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
title_full Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
title_fullStr Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
title_full_unstemmed Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
title_sort Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
author Sanches, Karoline [UNESP]
author_facet Sanches, Karoline [UNESP]
Dias, Raphael Vinicius Rodrigues [UNESP]
da Silva, Paulo Henrique [UNESP]
Fossey, Marcelo Andrés [UNESP]
Caruso, Ícaro Putinhon [UNESP]
de Souza, Fátima Pereira [UNESP]
de Oliveira, Leandro Cristante [UNESP]
de Melo, Fernando Alves [UNESP]
author_role author
author2 Dias, Raphael Vinicius Rodrigues [UNESP]
da Silva, Paulo Henrique [UNESP]
Fossey, Marcelo Andrés [UNESP]
Caruso, Ícaro Putinhon [UNESP]
de Souza, Fátima Pereira [UNESP]
de Oliveira, Leandro Cristante [UNESP]
de Melo, Fernando Alves [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Sanches, Karoline [UNESP]
Dias, Raphael Vinicius Rodrigues [UNESP]
da Silva, Paulo Henrique [UNESP]
Fossey, Marcelo Andrés [UNESP]
Caruso, Ícaro Putinhon [UNESP]
de Souza, Fátima Pereira [UNESP]
de Oliveira, Leandro Cristante [UNESP]
de Melo, Fernando Alves [UNESP]
dc.subject.por.fl_str_mv Biochemistry
Biomolecules
Biophysical chemistry
Biophysics
Coumarin
Fluorescence
Grb2
Molecular biology
Molecular docking
Molecular dynamics
Spectroscopy
STD-NMR
topic Biochemistry
Biomolecules
Biophysical chemistry
Biophysics
Coumarin
Fluorescence
Grb2
Molecular biology
Molecular docking
Molecular dynamics
Spectroscopy
STD-NMR
description Grb2 is an important regulator of normal vs. oncogenic cell signaling transduction. It plays a pivotal role on kinase-mediated signaling transduction by linking Receptor Tyrosine kinases to Ras/MAPK pathway which is known to bring oncogenic outcome. Coumarins are phenolic molecules found in several plants and seeds widely studied because of the antibiotic, anti-inflammatory, anticoagulant, vasodilator, and anti-tumor properties. Despite several studies about the anti-tumor properties of Coumarin in vivo and the role of Grb2 in signaling pathways related to cell proliferation, a molecular level investigation of the interaction between Grb2 and Coumarin is still missing. In this study, we performed a combined set of biophysical approaches to get insights on the interaction between Grb2 in a dimer state and Coumarin. Our results showed that Coumarin interacts with Grb2 dimer through its SH2 domain. The interaction is entropically driven, 1:1 molecular ratio and presents equilibrium constant of 105 M−1. In fact, SH2 is a well-known domain and a versatile signaling module for drug targeting which has been reported to bind compounds that block Ras activation in vivo. Despite we don't know the biological role coming from interaction between Grb2-SH2 domain and Coumarin, it is clear that this molecule could work in the same way as a SH2 domain inhibitor in order to block the link of Receptor Tyrosine kinases to Ras/MAPK pathway.
publishDate 2019
dc.date.none.fl_str_mv 2019-11-01
2020-12-12T02:30:19Z
2020-12-12T02:30:19Z
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.heliyon.2019.e02869
Heliyon, v. 5, n. 11, 2019.
2405-8440
http://hdl.handle.net/11449/201350
10.1016/j.heliyon.2019.e02869
2-s2.0-85075511597
3313511334783986
9768988416042770
0000-0002-4731-4977
0000-0002-8676-3150
url http://dx.doi.org/10.1016/j.heliyon.2019.e02869
http://hdl.handle.net/11449/201350
identifier_str_mv Heliyon, v. 5, n. 11, 2019.
2405-8440
10.1016/j.heliyon.2019.e02869
2-s2.0-85075511597
3313511334783986
9768988416042770
0000-0002-4731-4977
0000-0002-8676-3150
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Heliyon
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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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