Functional caracterization of FPPS/GGPPS isoforms in p. falciparum

• Grant number: 16/12649-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2016
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Alejandro Miguel Katzin
• Grantee: Gabriela Carolina Fernandes Leite
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malaria is one of the major human parasitosis, which consists in an important health problem worldwide, especially in african countries. There are many efforts going on with the intuit of develop new treatments and drugs against the disease. The lack of efficient vaccines and the parasite resistance to drugs are contributing to the delay of the control of this infection. The search for new biological targets is concerned, in general, with the metabolic paths research. One of the approaches is the functional characterization of essential enzymes in the formation of major precursors and secondary products. By studies in the intraerythrocytic stages of Plasmodium falciparum of the isoprenoids pathway it was characterized an important bifunctionalenzyme, the farnesyl pyrophosphate synthase/geranylgeranyl pyrophosphate synthase(FPPS/GGPPS) which is capable to form farnesyl diphosphate and geranylgeranyl pyrophosphate, two essential precursors to the biosynthesis of ubiquinone, menaquinone, carotenoids, dolichol and proteins isoprenylation. It was demonstrated differentiation of the enzyme localization along the intraeritrocitic cycle and that this enzyme presents lots of isoforms that possibly play different roles on regulation and alteration in one or more function of the enzyme. The objective of this project is to study the two isoforms of FPPS/GGPPS which lose important domains previously related with the activity of the enzyme, and determine a possible loss of some functions of the FPPS/GGPPS.