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Structural studies of enzymes involved in vitamin B1 and B6 synthesis in Plasmodium

Grant number: 19/20219-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2019
Effective date (End): October 31, 2021
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Alessandro Silva Nascimento
Grantee:Luana Galvão Morão
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:15/26722-8 - Drug discovery against human infectious diseases, AP.TEM


Malaria is a serious neglected disease and is still a worrying challenge as infected individuals are increasingly finding it difficult to get effectively cured. Among other factors, the resistance acquired by various microorganisms, including Malaria-causing Plasmodium species, has led to treatment difficulties and, in many cases, reduced the effectiveness of existing drugs. In this scenario, it is necessary to evaluate new potential molecular targets for the design of new drugs, as well as to propose new bioactive molecules for the treatment of this disease that affects more than 200 million individuals worldwide. An interesting strategy for the evaluation of new molecular targets is the inhibition of de novo biosynthesis of vitamins in the parasite. Since some of these pathways are present in Plasmodium and absent in humans, they constitute interesting targets with specific and selective action potential. In this project, we propose structural studies on the de novo biosynthesis pathway enzymes of vitamins B1 and B6, thiamine and pyridoxal, respectively. The proposal involves the cloning, expression and purification of enzymes involved in the biosynthetic routes of vitamins B1 and B6 in Plasmodium falciparum and Plasmodium vivax. Once determined, they can be used to screen potential inhibitory ligands on the vitamin biosynthesis pathway, compromising the viability of the parasite. (AU)