STRUCTURAL STUDIES OF PROTEINS INVOLVED TO LOCAL MUSCULAR NECROSIS IN BOTHROPIC ACCIDENTS

• Grant number: 15/24167-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2016
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Marcos Roberto de Mattos Fontes
• Grantee: Guilherme Henrique Marchi Salvador
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Envenoming caused by snakebites is considered a public health problem in many tropical and subtropical countries and has recently been included in the list of Neglected Tropical Diseases by the World Health Organization. In Latin America, accidents caused by snakes from Bothrops genus deserves special attention, since this group causes approximately 85% of reported accidents. One of the main complications regarding bothropic envenomation is the prominent local muscle damage caused by the bite of these snakes, deserving special attention the activity played by some classes of proteins. One of them consists of phospholipases A2 (PLA2s) and PLA2s-like, that act directly in the muscle membrane damaging it. Another group is constituted for metalloproteases (MPs) that are known by their ability to interfere with different components of the basal membrane, leading to hemorrhage. In this work we propose biophysical (Isothermal Titration Calorimetry, Small Angle X-ray Scattering and X-ray Crystallography) and functional studies with both classes of proteins because the lesion caused by them cannot be prevented or reverted by serum therapy administration. We are proposing to perform X-ray structural studies with these classes of toxins complexed to inhibitors already known in the literature aiming a better comprehension of the structural bases of the mechanisms underlying their inhibition. We also aim to identifies new ligands that may become potential inhibitors for these proteins from bothropic venom.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SALVADOR, GUILHERME H. M.; DOS SANTOS, JULIANA I.; LOMONTE, BRUNO; FONTES, MARCOS R. M.. Crystal structure of a phospholipase A(2) from Bothrops asper venom: Insights into a new putative "myotoxic cluster". Biochimie, v. 133, p. 8-pg., 2017-02-01. (15/17286-0, 15/24167-7)

SALVADOR, GUILHERME H. M.; DOS SANTOS, JULIANA I.; LOMONTE, BRUNO; FONTES, MARCOS R. M.. Crystal structure of a phospholipase A(2) from Bothrops asper venom: Insights into a new putative ``myotoxic cluster{''}. Biochimie, v. 133, p. 95-102, FEB 2017. (15/24167-7, 15/17286-0)