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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.)

Neutralization of a bothropic PLA(2)-like protein by caftaric acid, a novel potent inhibitor of ophidian myotoxicity

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Author(s):
Cardoso, Fabio F. [1] ; Gomes, Antoniel A. S. [1] ; Dreyer, Thiago R. [1] ; Cavalcante, Walter L. G. [2, 1, 3] ; Dal Pai, Maeli [4] ; Gallacci, Marcia [2] ; Fontes, Marcos R. M. [1]
Total Authors: 7
Affiliation:
[1] Univ Estadual Paulista UNESP, Inst Biociencias, Dept Fis & Biofis, Rua Prof Doutor Antonio Celso Wagner Zanin 250, Botucatu, SP - Brazil
[2] Univ Estadual Paulista UNESP, Inst Biociencias, Dept Farmacol, Botucatu, SP - Brazil
[3] Univ Fed Minas Gerais, Dept Farmacol, Inst Ciencias Biol, Belo Horizonte, MG - Brazil
[4] Univ Estadual Paulista UNESP, Inst Biociencias, Dept Morfol, Botucatu, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Biochimie; v. 170, p. 163-172, MAR 2020.
Web of Science Citations: 0
Abstract

Envenoming by snakebite is an important global health issue that has received little attention, leading the World Health Organization to naming it as neglected tropical disease. Several snakebites present serious local symptoms manifested on victims that may not be efficiently neutralized by serum therapy. Phospholipase A(2)-like (PLA(2)-like) toxins are present in Viperidae venoms and are responsible for local myotoxic activity. Herein, we investigated the association between BthTX-I toxin and caftaric acid (CFT), a molecule present in plants. CFT neutralized neuromuscular blocking and muscle-damaging activities promoted by BthTX-I. Calorimetric and light-scattering assays demonstrated that CFT inhibitor interacted with dimeric BthTX-I. Bioinformatics simulations indicated that CFT inhibitor binds to the toxin's hydrophobic channel (HCh). According to the current myotoxic mechanism, three different regions of PLA(2)-like toxins have specific tasks: protein allosteric activation (HCh), membrane dockage (MDoS), and membrane rupture (MDiS). We propose CFT inhibitor interferes with the allosteric activation, which is related to the conformation change leading to the exposure/alignment of MDoS/MDiS region. This is the first report of a PLA(2)-like toxin fully inhibited by a compound that interacts only with its HCh region. Thus, CFT is a novel candidate to complement serum therapy and improve the treatment of snakebite. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

FAPESP's process: 12/07112-6 - Structural and functional studies with Bothropstoxin-I, from Bothrops jararacussu snake venom, and caffeic acid derivates
Grantee:Fábio Florença Cardoso
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 15/17286-0 - Structural and functional studies aiming to understand the role of snake venoms toxins and how to inhibit their biological activity
Grantee:Marcos Roberto de Mattos Fontes
Support Opportunities: Regular Research Grants