Molecular cloning and structural modelling of gamma-phospholipase A2 inhibitors from Bothrops atrox and Micrurus lemniscatus snakes

Abstract

Phospholipases A2inhibitors (PLIs) produced by venomous and non-venomous snakes play essentialrole in this resistance. These endogenous inhibitors may be classified by their fold in PLI , PLI andPLI . Phospholipases A2(PLA2s) develop myonecrosis in snake envenomation, a consequence that isnot efficiently neutralized by antivenom treatment. This work aimed to identify and characterize twoPLIs from Amazonian snake species, Bothrops atrox and Micrurus lemniscatus. Liver tissues RNA of speci-mens from each species were isolated and amplified by RT-PCR using PCR primers based on known PLI gene sequences, followed by cloning and sequencing of amplified fragments. Sequence similarity studiesshowed elevated identity with inhibitor PLI gene sequences from other snake species. Molecular modelsof translated inhibitors’ gene sequences resemble canonical three finger fold from PLI and support thehypothesis that the decapeptide (residues 107–116) may be responsible for PLA2inhibition. Structuralstudies and action mechanism of these PLIs may provide necessary information to evaluate their potentialas antivenom or as complement of the current ophidian accident treatment