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Structural studies of complexes between bothropic myotoxins and hydroxycinnamic inhibitors

Grant number: 14/19283-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2014
Effective date (End): December 31, 2016
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Marcos Roberto de Mattos Fontes
Grantee:Eloah dos Santos de Biasi
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The snake bite envenomation is a public health problem in many tropical and subtropical countries and was recently included in the list of Neglected Tropical Diseases by the World Health Organization. In Brazil occurs more than twenty thousand accidents with snakes per year, of which approximately 90% accidents involve Bothrops. The Bothrops snakebites cause local changes such as pain, swelling and intense myonecrosis. The only available treatment is antivenom, however, it is not fully effective in the recovery of local damage and, in some cases, cannot avoid the amputation of limbs and consequent disabling of the victim. The objective of this project is to study, through protein crystallography, the interaction between phospholipase A2-like (PLA2) that with the metalloproteinases are the main responsible for myonecrosis process. Therefore, we propose the co-crystallization of Bothropstoxin-I (BthTX-I), an isolated Lys49-PLA2 from Bothrops jararacussu venom, and plant ligandsinhibitors, such as cinnamic acid, p-coumaric acid, ferulic acid, chlorogenic acid, caftaric acid and chicoric acid in order to obtain myotoxic inhibitor. This study is part of research field by the Laboratory of Molecular Structural Biology in the last 15 years, being published more than 50 articles that were cited extensively by the international scientific community. Currently, in our group there are two post-doctoral fellows from FAPESP, five doctoral students and one master student in this research that have been constantly supported by projects of FAPESP, CNPq and CAPES.