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

The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis

Full text
Author(s):
Eberle, Raphael J. [1] ; Coronado, Monika A. [1] ; Peinado, Rafaela S. [1] ; de Moraes, Fabio R. [1] ; Olivier, Danilo [1] ; Dreyer, Thiago [2] ; Lopes, Debora de Oliveira [3] ; Rosa da Luz, Brenda Silva [4] ; Azevedo, Vasco [4] ; Arni, Raghuvir K. [1]
Total Authors: 10
Affiliation:
[1] Univ Estadual Paulista UNESP, Inst Biociencias Letras & Ciencias Exatas Ibilce, Dept Phys, Multiuser Ctr Biomol Innovat, Rua Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Univ Estadual Paulista Julio de Mesquita Filho UN, Inst Biociencias, Dept Fis & Biofis, Botucatu, SP - Brazil
[3] Univ Fed Sao Joao Del Rei CCO, Mol Biol Lab, Ave Sebastiao Goncalves Coelho 400, BR-35501296 Divinopolis, MG - Brazil
[4] Univ Fed Minas Gerais, Inst Ciencias Biol, Lab Genet Celular & Mol, Ave Antonio Carlos, 6627 Pampulha, CP 486, BR-31270901 Belo Horizonte, MG - Brazil
Total Affiliations: 4
Document type: Journal article
Source: International Journal of Biological Macromolecules; v. 125, p. 459-468, MAR 15 2019.
Web of Science Citations: 0
Abstract

Currently no effective treatment is available to combat infections caused by Corynebacterium pseudotuberculosis in livestock. Survival of this Gram-positive bacterium in rapidly-growing pathogens in hostile environments is strongly dependent on the existence of a robust DNA repair system to prevent DNA mutations and contribute to bacterial colonization and virulence. The adenine/guanine-specific DNA glycosylase (MutY) is evolutionarily conserved and has been well characterized due to its central role in the prevention of mutagenesis and DNA repair. The aim of this study was the characterization of the target protein interaction with free adenine, suramin, and heparin, as well as the binding competition characterization between the molecules. The dissociation constant for free adenine interaction with Corynebacterium pseudotuberculosis MutY (Cp-MutY) was determined, 86 +/- 2.5 mu M. NMR competition experiments demonstrated, that the polyanions heparin and suramin compete with adenine for the protein active site. The determined dissociation constant for the heparin/Cp-MutY interaction was 5.9 +/- 1.0 mu M and for suramin was 16 +/- 1.5 mu M. Docking of both polyanions with Cp-MutY revealed a possible mode of interaction and indicates that these molecules can interfere with the protein interaction with damaged DNA or prevent the binding of the adenine base in the enzyme active site. (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