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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Oxidative Alteration of Trp-214 and Lys-199 in Human Serum Albumin Increases Binding Affinity with Phenylbutazone: A Combined Experimental and Computational Investigation

Texto completo
Autor(es):
Bertozo, Luiza de Carvalho [1] ; Neto, Ernesto Tavares [2] ; de Oliveira, Leandro Cristante [2] ; Ximenes, Valdecir Farias [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] UNESP Sao Paulo State Univ, Dept Chem, Fac Sci, BR-17033360 Bauru, SP - Brazil
[2] UNESP Sao Paulo State Univ, Dept Phys, Inst Biosci Humanities & Exact Sci, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 19, n. 10 OCT 2018.
Citações Web of Science: 0
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. (AU)

Processo FAPESP: 14/50926-0 - INCT 2014: biodiversidade e produtos naturais
Beneficiário:Vanderlan da Silva Bolzani
Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
Processo FAPESP: 16/20549-5 - Desenvolvimento e aplicação de sondas fluorescentes e baseadas em dicroísmo circular para estudos de interação de ligantes com proteínas, caracterização de proteínas amiloides e determinação de atividade enzimática
Beneficiário:Valdecir Farias Ximenes
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/22014-1 - Desenvolvimento de sondas fluorescentes para determinação de sítios de ligação em albumina: estudo da relação entre estrutura molecular, constante de associação e especificidade
Beneficiário:Luiza de Carvalho Bertozo
Linha de fomento: Bolsas no Brasil - Doutorado