Structural and evolutionary insights into endogenous alpha-phospholipase A2 inhibitors of Latin American pit vipers

• Autor(a) principal: Estevão-Costa, Maria Inácia
• Data de Publicação: 2016
• Outros Autores: Fernandes, Carlos Alexandre H. [UNESP], Mudadu, Maurício De Alvarenga, Franco, Glória Regina, Fontes, Marcos Roberto M. [UNESP], Fortes-Dias, Consuelo Latorre
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.toxicon.2016.01.058; http://hdl.handle.net/11449/168365
• topic: Phospholipase A2; Phospholipase A2 inhibitor; PLA2; PLI; Snake; Viperidae

Phospholipases A2 are major components of snake venoms (svPLA2s) and are able to induce multiple local and systemic deleterious effects upon envenomation. Several snake species are provided with svPLA2 inhibitors (sbPLIs) in their circulating blood, which confer a natural resistance against the toxic components of homologous and heterologous venoms. The sbPLIs belong to any of three structural classes named α, β and γ. In the present study, we identified, characterized and performed structural and evolutionary analyses of sbαPLIs transcripts and the encoded proteins, in the most common Latin American pit vipers belonging to Crotalus, Bothrops and Lachesis genera. Mutation data indicated that sbαPLIs from Latin American snakes might have evolved in an accelerated manner, similarly to that reported for sbαPLIs from Asian snakes, and possibly co-evoluted with svPLA2s in response to the diversity of target enzymes. The importance of sbαPLI trimerization for the effective binding and inhibition of acidic svPLA2s is discussed and conserved cationic residues located at the central pore of the inhibitor trimer are suggested to be a significant part of the binding site of sbαPLIs to acidic svPLA2s. Our data contribute to the current body of knowledge on the structural and evolutionary characteristics of sbPLIs, in general, and may assist in the future development of selective inhibitors for secretory PLA2 from several sources.