Citation

Fernandes CA, Comparetti EJ, Borges RJ, Huancahuire-Vega S, Ponce-Soto LA, Marangoni S, Soares AM, Fontes MRM. Biochim. Biophys. Acta 2013; 1834(12): 2772-2781.

Affiliation

Dep. de Física e Biofísica, Instituto de Biociências, UNESP - Universidade Estadual Paulista, Botucatu-SP and Instituto Nacional de Ciência e Tecnologia em Toxinas, CNPq, Brazil.

Copyright

(Copyright © 2013, Elsevier Publishing)

DOI

10.1016/j.bbapap.2013.10.009

PMID

24145104

Abstract

Bothrops brazili is a snake found in the forests of the Amazonian region whose commercial therapeutic anti-bothropic serum has low efficacy for local myotoxic effects, resulting in an important public health problem in this area. Catalytically inactive phospholipases A2-like (Lys49-PLA2s) are among the main components from Bothrops genus venoms and are capable to cause drastic myonecrosis. Several studies have shown that the C-terminal region of these toxins, which includes a variable combination of positively charged and hydrophobic residues, is responsible for their activity. In this work we describe the crystal structures of two Lys49-PLA2s (BbTX-II and MTX-II) from Bothrops brazili venom and a comprehensive structural comparison with several Lys49-PLA2s. Based on these results, it was identified two independent sites of interaction between protein and membrane which leads to the proposition of a new myotoxic mechanism for bothropic Lys49-PLA2s composed by five different steps. This proposition is able to fully explain the action of these toxins and may be useful to develop efficient inhibitors for complement the conventional antivenom administration.

Language: en