Diversity of metalloproteinases in Bothrops neuwiedi snake venom: structural and functional variability and identification of toxins responsible for hemostatic disturbances

• Grant number: 10/11330-3
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2010 - October 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Ana Maria Moura da Silva
• Grantee: Ana Maria Moura da Silva
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Cristiani Baldo da Rocha ; Geraldo Santana Magalhães

Abstract

Snake venom metalloproteinases (SVMPs) are widely distributed in venoms of viper snakes and are involved in several symptoms following snake bite. SVMPs hydrolyze plasma and extracellular matrix proteins and also interact with surface receptors of platelets, endothelial and inflammatory cells activating or inhibiting their functions. The functional versatility of SVMPs is strongly related to their structural diversity generated by the accelerated evolution of this family of proteins. In order to understand the generation of functional and structural diversity of SVMPs, we have recently started in our laboratory studies with venoms of Bothrops neuwiedi snakes. Analyzing cDNAs cloned from the venom glands, we detected sequences coding for SVMPs belonging to P-I, P-II and P-III classes, some of them with different domain structure than the previously described ones. In this project, we aim to analyze the relationships among these sequences and other SVMPs already described in viper venoms intending to understand evolutionary mechanisms involved in the generation of diversity. The novel SVMPs detected by cDNA sequencing will be isolated from the venom or obtained by expression of the corresponding cDNAs in mammalian systems. Isolated proteins will be tested for the action and mechanisms involved in the hemostatic disorders induced by snake venoms. With these approaches, we intend to elucidate generation of structural and functional diversity of SVMPs and describe novel SVMPs with distinct functions in hemostatic disturbances. (AU)