Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
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. |
id |
UNSP_3fc43adb1d228479a10b4b75e53b4cac |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/201350 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
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 |
|
_version_ |
1808128280478351360 |