Abstract
The mortality caused by snakebites is more damaging than many tropical diseases, such as dengue haemorrhagic fever, cholera, leishmaniasis, schistosomiasis and Chagas disease. For this reason, snakebite envenoming adversely affects health services of tropical and subtropical countries and is recognized as a neglected disease by the World Health Organization. One of the main components of snake venoms is the Lys49-phospholipases A2, which is catalytically inactive but possesses other toxic and pharmacological activities. Preliminary studies with MjTX-I from Bothrops moojeni snake venom revealed intriguing new structural and functional characteristics compared to other bothropic Lys49-PLA2s. We present in this article a comprehensive study with MjTX-I using several techniques, including crystallography, small angle X-ray scattering, analytical size-exclusion chromatography, dynamic light scattering, myographic studies, bioinformatics and molecular phylogenetic analyses.Based in all these experiments we demonstrated that MjTX-I is probably a unique Lys49-PLA2, which may adopt different oligomeric forms depending on the physical-chemical environment. Furthermore, we showed that its myotoxic activity is dramatically low compared to other Lys49-PLA2s, probably due to the novel oligomeric conformations and important mutations in the C-terminal region of the protein. The phylogenetic analysis also showed that this toxin is clearly distinct from other bothropic Lys49-PLA2s, in conformity with the peculiar oligomeric characteristics of MjTX-I and possible emergence of new functionalities inresponse to environmental changes and adaptation to new preys.
Highlights
Snakes are one of the major groups of the Squamata reptilian order, with more than 3300 extant and extinct species already identified by the scientific community [1]
This fact has attracted massive attention from the scientific community resulting in the publication of some important articles and reviews about the real impact of the snakebites on health services [2,3,4] and, recently, snakebite accidents were classified as a neglected disease by the World Health Organization (WHO) [3]
As in other Lys49-PLA2s structures, two of them are close to His48 in monomers A and B, and the third polyethylene glycol (PEG) 4000 molecule is sited between the interface of the monomers A and B
Summary
Snakes are one of the major groups of the Squamata reptilian order, with more than 3300 extant and extinct species already identified by the scientific community [1] Many of these animals are venomous and represent an important public health problem in rural areas of Asia, Africa and Latin America. It was attested that the mortality caused by snakebites is higher than other neglected tropical diseases, such as dengue haemorrhagic fever, cholera, leishmaniasis, schistosomiasis and Chagas disease [2] This fact has attracted massive attention from the scientific community resulting in the publication of some important articles and reviews about the real impact of the snakebites on health services [2,3,4] and, recently, snakebite accidents were classified as a neglected disease by the World Health Organization (WHO) [3].
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