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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids

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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]
Total Authors: 8
[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
Total Affiliations: 3
Document type: Journal article
Source: International Journal of Biological Macromolecules; v. 117, p. 1066-1073, OCT 1 2018.
Web of Science Citations: 0

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)

FAPESP's process: 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules
Grantee:Raghuvir Krishnaswamy Arni
Support type: Multi-user Equipment Program
FAPESP's process: 15/18868-2 - Multi-user equipment acquisition for molecular and structural biology
Grantee:Raghuvir Krishnaswamy Arni
Support type: Multi-user Equipment Program
FAPESP's process: 16/08104-8 - Structural and functional aspects of two DNA binding proteins encoded by Corynebacterium pseudotuberculosis
Grantee:Raphael Josef Eberle
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/13765-0 - Structural Studies and Characterization of Proteins by X-ray Crystallography and Nuclear Magnetic Resonance. Structural investigations and biophysics of molecular mechanisms of functional proteins.
Grantee:Raghuvir Krishnaswamy Arni
Support type: Regular Research Grants
FAPESP's process: 16/12904-0 - Mechanism and Molecular Interactions of Bioactive molecules with NS3 protease from Zika virus.
Grantee:Monika Aparecida Coronado
Support type: Scholarships in Brazil - Post-Doctorate