Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids

Autor(es)

Eberle, Raphael J. ^[1] ; Kawai, Liege A. ^[1] ; de Moraes, Fabio R. ^[1] ; Olivier, Danilo ^[1] ; do Amaral, Marcos S. ^[2] ; Tasic, Ljubica ^[3] ; Ami, Raghuvir K. ^[1] ; Coronado, Monika A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista UNESP, Inst Biociencias Letras & Ciencias Exatas Ibilce, Multiuser Ctr Biomol Innovat, Dept Phys, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Fed Mato Grosso do Sul, Inst Phys, BR-79090700 Campo Grande, MS - Brazil

^[3] Univ Campinas UNICAMP, Inst Chem, Chem Biol Lab, Organ Chem Dept, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 117, p. 1066-1073, OCT 1 2018.
• Citações Web of Science: 0

Resumo

In pathogens, the thioredoxin system forms part of the defense against oxidative stress and ensures the formation of the proper disulfide bonds to ensure protein function. In Corynebacterium pseudotuberculosis, the role and mechanism of TrxA1 has not been elucidated, but, the significant homology among different Trxs and the conservation of the residues that form their active sites underline the importance of the Trx systems. Proteins involved in redox metabolism and low molecular weight thiols, which might interact with them, become attractive targets to modulate the activity of pathogens. The activity of the protein was investigated using a turbidimetric assay system. The influence of different pH and low molecular weight thiols were tested. Additionally, this assay was used to investigate the inhibitory potential of ligands from different molecular families, such as, polyanions (suramin and heparin) and flavonoids (hesperetin and hesperidin). All four compounds showed inhibition of the protein activity by approximately 80%. The interactions between these compounds and Cp-TrxA1 were investigated using CD spectroscopy, NMR, molecular docking and dynamics. Our results demonstrate that suramin and hesperetin can serve as lead molecules for the development of specific inhibitors for the C. pseudotuberculosis TrxA1. (C) 2018 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 09/53989-4 - EMU: aquisição de espectrômetro de ressonância magnética nuclear para estudos de biomoléculas
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 15/18868-2 - Aquisição de equipamento multiusuário para biologia molecular e estrutural
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 16/08104-8 - Aspectos funcionais e estruturais de duas proteínas de ligação de DNA codificadas pela Corynebacterium pseudotuberculosis
• Beneficiário: Raphael Josef Eberle
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/13765-0 - ESTUDOS ESTRUTURAIS E CARACTERIZAÇÃO DE PROTEÍNAS POR CRISTALOGRAFIA DE RAIOS-X E RESSONÂNCIA MAGNETICA NUCLEAR. Investigações estruturais e biofísicas dos mecanismos moleculares de proteínas funcionais
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/12904-0 - Mecanismos e Interações Moleculares de Moléculas Bioativas com a Protease NS3 do Zika Vírus.
• Beneficiário: Monika Aparecida Coronado
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado