Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/ijms19102868 http://hdl.handle.net/11449/189763 |
Resumo: | Human serum albumin (HSA) is a target for reactive oxygen species (ROS), and alterations of its physiological functions caused by oxidation is a current issue. In this work, the amino-acid residues Trp-214 and Lys-199, which are located at site I of HSA, were experimentally and computationally oxidized, and the effect on the binding constant with phenylbutazone was measured. HSA was submitted to two mild oxidizing reagents, taurine monochloramine (Tau-NHCl) and taurine dibromamine (Tau-NBr2). The oxidation of Trp-214 provoked spectroscopic alterations in the protein which were consistent with the formation of N′-formylkynurenine. It was found that the oxidation of HSA by Tau-NBr2, but not by Tau-NHCl, provoked a significant increase in the association constant with phenylbutazone. The alterations of Trp-214 and Lys-199 were modeled and simulated by changing these residues using the putative oxidation products. Based on the Amber score function, the interaction energy was measured, and it showed that, while native HSA presented an interaction energy of −21.3 kJ/mol, HSA with Trp-214 altered to N′-formylkynurenine resulted in an energy of −28.4 kJ/mol, and HSA with Lys-199 altered to its carbonylated form resulted in an energy of −33.9 kJ/mol. In summary, these experimental and theoretical findings show that oxidative alterations of amino-acid residues at site I of HSA affect its binding efficacy. |
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Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigationAlbuminN′-formylkynurenineOxidative stressPhenylbutazoneTaurine dibromamineTryptophanHuman serum albumin (HSA) is a target for reactive oxygen species (ROS), and alterations of its physiological functions caused by oxidation is a current issue. In this work, the amino-acid residues Trp-214 and Lys-199, which are located at site I of HSA, were experimentally and computationally oxidized, and the effect on the binding constant with phenylbutazone was measured. HSA was submitted to two mild oxidizing reagents, taurine monochloramine (Tau-NHCl) and taurine dibromamine (Tau-NBr2). The oxidation of Trp-214 provoked spectroscopic alterations in the protein which were consistent with the formation of N′-formylkynurenine. It was found that the oxidation of HSA by Tau-NBr2, but not by Tau-NHCl, provoked a significant increase in the association constant with phenylbutazone. The alterations of Trp-214 and Lys-199 were modeled and simulated by changing these residues using the putative oxidation products. Based on the Amber score function, the interaction energy was measured, and it showed that, while native HSA presented an interaction energy of −21.3 kJ/mol, HSA with Trp-214 altered to N′-formylkynurenine resulted in an energy of −28.4 kJ/mol, and HSA with Lys-199 altered to its carbonylated form resulted in an energy of −33.9 kJ/mol. In summary, these experimental and theoretical findings show that oxidative alterations of amino-acid residues at site I of HSA affect its binding efficacy.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Chemistry Faculty of Sciences UNESP–São Paulo State UniversityDepartment of Physics Institute of Biosciences Humanities and Exact Sciences UNESP–São Paulo State UniversityDepartment of Chemistry Faculty of Sciences UNESP–São Paulo State UniversityDepartment of Physics Institute of Biosciences Humanities and Exact Sciences UNESP–São Paulo State UniversityFAPESP: # 2014/50926-0FAPESP: # 2016/20549-5FAPESP: # 2016/22014-1CNPq: # 302793/2016-0CNPq: #442352/2014-0Universidade Estadual Paulista (Unesp)Bertozo, Luiza de Carvalho [UNESP]Tavares Neto, Ernesto [UNESP]de Oliveira, Leandro Cristante [UNESP]Ximenes, Valdecir Farias [UNESP]2019-10-06T16:51:23Z2019-10-06T16:51:23Z2018-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/ijms19102868International Journal of Molecular Sciences, v. 19, n. 10, 2018.1422-00671661-6596http://hdl.handle.net/11449/18976310.3390/ijms191028682-s2.0-85053833105Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Sciencesinfo:eu-repo/semantics/openAccess2024-04-29T18:17:11Zoai:repositorio.unesp.br:11449/189763Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:38:17.812079Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation |
title |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation |
spellingShingle |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation Bertozo, Luiza de Carvalho [UNESP] Albumin N′-formylkynurenine Oxidative stress Phenylbutazone Taurine dibromamine Tryptophan |
title_short |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation |
title_full |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation |
title_fullStr |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation |
title_full_unstemmed |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation |
title_sort |
Oxidative alteration of Trp-214 and Lys-199 in human serum albumin increases binding affinity with phenylbutazone: A combined experimental and computational investigation |
author |
Bertozo, Luiza de Carvalho [UNESP] |
author_facet |
Bertozo, Luiza de Carvalho [UNESP] Tavares Neto, Ernesto [UNESP] de Oliveira, Leandro Cristante [UNESP] Ximenes, Valdecir Farias [UNESP] |
author_role |
author |
author2 |
Tavares Neto, Ernesto [UNESP] de Oliveira, Leandro Cristante [UNESP] Ximenes, Valdecir Farias [UNESP] |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Bertozo, Luiza de Carvalho [UNESP] Tavares Neto, Ernesto [UNESP] de Oliveira, Leandro Cristante [UNESP] Ximenes, Valdecir Farias [UNESP] |
dc.subject.por.fl_str_mv |
Albumin N′-formylkynurenine Oxidative stress Phenylbutazone Taurine dibromamine Tryptophan |
topic |
Albumin N′-formylkynurenine Oxidative stress Phenylbutazone Taurine dibromamine Tryptophan |
description |
Human serum albumin (HSA) is a target for reactive oxygen species (ROS), and alterations of its physiological functions caused by oxidation is a current issue. In this work, the amino-acid residues Trp-214 and Lys-199, which are located at site I of HSA, were experimentally and computationally oxidized, and the effect on the binding constant with phenylbutazone was measured. HSA was submitted to two mild oxidizing reagents, taurine monochloramine (Tau-NHCl) and taurine dibromamine (Tau-NBr2). The oxidation of Trp-214 provoked spectroscopic alterations in the protein which were consistent with the formation of N′-formylkynurenine. It was found that the oxidation of HSA by Tau-NBr2, but not by Tau-NHCl, provoked a significant increase in the association constant with phenylbutazone. The alterations of Trp-214 and Lys-199 were modeled and simulated by changing these residues using the putative oxidation products. Based on the Amber score function, the interaction energy was measured, and it showed that, while native HSA presented an interaction energy of −21.3 kJ/mol, HSA with Trp-214 altered to N′-formylkynurenine resulted in an energy of −28.4 kJ/mol, and HSA with Lys-199 altered to its carbonylated form resulted in an energy of −33.9 kJ/mol. In summary, these experimental and theoretical findings show that oxidative alterations of amino-acid residues at site I of HSA affect its binding efficacy. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-10-01 2019-10-06T16:51:23Z 2019-10-06T16:51:23Z |
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/10.3390/ijms19102868 International Journal of Molecular Sciences, v. 19, n. 10, 2018. 1422-0067 1661-6596 http://hdl.handle.net/11449/189763 10.3390/ijms19102868 2-s2.0-85053833105 |
url |
http://dx.doi.org/10.3390/ijms19102868 http://hdl.handle.net/11449/189763 |
identifier_str_mv |
International Journal of Molecular Sciences, v. 19, n. 10, 2018. 1422-0067 1661-6596 10.3390/ijms19102868 2-s2.0-85053833105 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Molecular Sciences |
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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1808129230361329664 |