Structural studies with snake venom toxins from Amazon region

• Grant number: 13/10611-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2013
• End date: July 31, 2014
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Marcos Roberto de Mattos Fontes
• Grantee: Edson José Comparetti
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The snake bite poisoning is a public health problem in many tropical and subtropical countries and was recently included in the list of the Neglected Tropical Diseases World Health Organization. In Latin America, the vast majority of accidents are caused by snakes of the Bothrops and Crotalus. One of the main problems associated with Bothrops poisoning is the prominent local damage caused by the bite of these snakes, and the phospholipase A2 and metalloproteinases are the major constituents. In this project, we propose that the student works with phospholipase A2 (PLA2s) and phospholipase A2 homologues (Lys49-PLA2s) from the venom of a serpent Amazon (Bothrops brazili) little studied functionally and structurally, since most studies are done with snakes originating from the rainforest or savanna. The structural analysis of proteins of this poison was started about two years in our laboratory and allowed to crystallize three PLA2s with myotoxic activity (two Lys49-PLA2 and one PLA2) with the publication of an article in the journal Acta Crustallogaphica in 2012 in which the student is coauthor. In the project we are proposing the conclusion of refinement/modeling and structural analysis of both Lys49-PLA2 (MT-II and BbTX-II) with subsequent writing of a scientific paper. The student also will work with the optimization of crystals, X-ray diffraction data collection, refinement/modeling and structural analysis of the catalytic and myotoxic PLA2 (BbTX-III). The student selected to develop the project works in the Laboratory of Molecular Structure (LBME) since the first half of their undergraduate degree and already has PIBIC-CNPq fellowship that end on August 2013; moreover, it has shown excellent performance in academic Medical Physics course, being one of the top students in his class. This project also allows the inclusion of the student in all techniques of protein crystallography (crystallization, elucidation, modeling, refinement, structural analysis and writing of a scientific paper) which may qualify him to act fully in the area that is lacking of qualified people. (AU)