Characterization of 1,4-dihydroxy-2-naphthoate preniltransferase (MenA) involved in the pathway of Vitamin K during the Intra-erythrocytic development of Plasmodium falciparum

• Grant number: 13/10105-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2013
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Alejandro Miguel Katzin
• Grantee: Heloisa Berti Gabriel
• Supervisor: Dean C. Crick
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Colorado State University, United States
• Associated to the scholarship: 10/19518-1 - Functional characterization of farnesyl pyrophosphate synthase (FPPs) and 1,4-dihydroxy-2-naftoato preniltransferase (MenA) respectively involved in the isoprenoid pathway and the vitamin K during the intra-erythrocytic development of P. falciparum, BP.DR

Abstract

Malaria is one of the leading and most widespread of human parasites, if constituting a serious health problem worldwide, especially in African countries. Many efforts have been deployed in recent years in order to develop new treatments and new chemotherapeutic agents against the disease. The lack of an effective vaccine and the problem of drug resistance has contributed to the postponement of the solution of the control of this infection. The search for new biological targets have focused in part on research and new understanding of the metabolic pathways, one of the approaches to enzyme characterization and localization of these new pathways, as well as the demonstration of having a key role in the cycle of the parasite. In P. falciparum identify the biosynthesis of the two forms of vitamin K (phylloquinone and menaquinone), from the shikimate and the MEP pathway, as well as biosynthesis of ubiquinone (UB7-8). Our studies have shown a possible role of respiratory chain MQ parasite under anaerobic conditions and their biosynthesis inhibition resulting from treatment with Ro 48-8071 (a drug that inhibits the enzyme encoded by the MenA gene in Mycobacterium tuberculosis in the biosynthesis of MQ) . This project has as main objective to characterize the gene MenA in the biosynthesis of MQ, possible target of the inhibitor Ro 48-8071 and test the effect of potential inhibitors of this enzyme that can act as potent antimalarials. The results generated will help you understand more about the mechanisms of survival of P. falciparum, thereby boosting, new targets for antimalarial drugs. (AU)