Molecular cloning and structural modelling of gamma-phospholipase A(2) inhibitors from Bothrops atrox and Micrurus lemniscatus snakes

作者：Picelli Carina G; Borges Rafael J; Fernandes Carlos A H; Matioli Fabio M; Fernandes Carla F C; Sobrinho Juliana C; Holanda Rudson J; Ozaki Luiz S; Kayano Anderson M; Calderon Leonardo A; Fontes Marcos R M; Stabeli Rodrigo G; Soares Andreimar M^*

来源：International Journal of Biological Macromolecules, 2017, 103: 525-532.

DOI：10.1016/j.ijbiomac.2017.05.076

• Snakes
• Bothrops atrox
• Micrurus lemniscatus
• Inhibitors of phospholipases A(2)
• Gamma type phospholipase A(2) inhibitors

Phospholipases A(2) inhibitors (PLIs) produced by venomous and non-venomous snakes play essential role in this resistance. These endogenous inhibitors may be classified by their fold in PLI alpha, PLI beta and PLI gamma. Phospholipases A(2) (PLA(2)s) develop myonecrosis in snake envenomation, a consequence that is not efficiently neutralized by antivenom treatment. This work aimed to identify and characterize two PLIs from Amazonian snake species, Bothrops atrox and Micrurus lemniscatus. Liver tissues RNA of specimens from each species were isolated and amplified by RT-PCR using PCR primers based on known PLI gamma gene sequences, followed by cloning and sequencing of amplified fragments. Sequence similarity studies showed elevated identity with inhibitor PLI gamma gene sequences from other snake species. Molecular models of translated inhibitors' gene sequences resemble canonical three finger fold from PLI gamma and support the hypothesis that the decapeptide (residues 107-116) may be responsible for PLA(2) inhibition. Structural studies and action mechanism of these PLIs may provide necessary information to evaluate their potential as antivenom or as complement of the current ophidian accident treatment.

• 出版日期2017-10
• 单位Univ Estadual Paulista