Structural and functional studies of native, recombinant and complexed proteins, from snake venom, with vegetable inhibitors

• Grant number: 12/06502-5
• Support type: Regular Research Grants
• Duration: September 01, 2012 - October 31, 2014
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Marcos Roberto de Mattos Fontes
• Grantee: Marcos Roberto de Mattos Fontes
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Assoc. researchers: Cristiano Luis Pinto de Oliveira ; Marcia Gallacci ; Ney Lemke
• Associated scholarship(s): 14/04425-9 - Structural and functional studies of native, recombinant and complexed proteins, from snake venom, with vegetable inhibitors, BP.TT; 12/24719-1 - Structural and functional studies of native, recombinant and complexed proteins, from snake venom, with vegetable inhibitors, BP.TT

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, the majority of ophidic accidents are caused by snakes from Bothrops and Crotalus genus. 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 two classes of proteins. One of them consists of phospholipases A2 that act directly in the muscle membrane damaging them. The other group is constituted of metalloproteases that are known by their ability to interfere with different components of the basal membrane, consequently leading to hemorrhage. In this work, we propose for the first time, a wide structural and functional study of snake venom proteins - native, recombinant and complexed to potential inhibitors. The following techniques will be used: protein crystallography, small angle X-ray scattering, circular dichroism, dynamic light scattering, affinity experiments (using isothermal titration calorimetry, analytical size exclusion chromatography, site-direct mutation, docking, molecular dynamics, phylogenetic analysis and in vitro functional studies including electrophysiology and myographic techniques followed by morphologic analysis (optic and electronic microscopy).This information could be very important for the identification, characterization and development (drug design) of substances with biotechnological and pharmacological use. These compounds may be used for the control of symptoms that cannot be prevented or reverted by serum therapy administration and, also, as aid the treatment of several pathological process. This project is a continuation of other projects already supported by FAPESP (four grants in the snake venom proteins field) and CNPq (three grants in the field) since 1997. Furthermore, the Laboratory is also supported by INCT in Toxinology (FAPESP/CNPq) and Toxinology project of the CAPES agency. The laboratory already published, only in the snake venom toxin field, more than 50 articles (it also develops research in other fields of Structural Biology) and finished 16 theses in the field. (AU)

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)

TOYAMA, DANIELA DE OLIVEIRA; GAETA, HENRIQUE HESSEL; TERASHIMA DE PINHO, MARCUS VINICIUS; PENA FERREIRA, MARCELO JOSE; ROMOFF, PAULETE; MATIOLI, FABIO FILIPPI; MAGRO, ANGELO JOSE; DE MATTOS FONTES, MARCOS ROBERTO; TOYAMA, MARCOS HIKARI. An Evaluation of 3-Rhamnosylquercetin, a Glycosylated Form of Quercetin, against the Myotoxic and Edematogenic Effects of sPLA(2) from Crotalus durissus terrificus. BIOMED RESEARCH INTERNATIONAL, 2014. Web of Science Citations: 3.