Structural characterization of vitamin B1 and B6 synthesis pathway enzymes in Plasmodium falciparum and Mycobacterium tuberculosis

• Grant number: 18/21213-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): January 01, 2019
• Effective date (End): November 26, 2022
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Alessandro Silva Nascimento
• Grantee: Angélica Luana Carrillo Barra
• Host 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
• Associated scholarship(s): 19/26428-3 - Analyzing structure, function and dynamics of vitamin B6 biosynthesis enzymes from Plasmodium vivax, BE.EP.DD

Abstract

Infectious diseases are a threat to humanity and currently its pathogens are spreading geographically due to globalization and the development of drug resistance available. The drug resistance currently available is occurring in almost all pathogens and therefore there is an urgent need to discover new therapeutic targets and/or new target classes. In this project the focus will be on the discovery of new prodrugs exploring the biosynthesis pathways of B1/B6 vitamins of human pathogens: Plasmodium falciparum, the parasite responsible for causing severe Malaria in addition to the responsible for Tuberculosis, Mycobacterium tuberculosis. For the design of compounds, the crystallographic structures of the respective enzymes involved in the biosynthesis of vitamins B1/B6 will be determined, aiming the incorporation of the compounds in the metabolism of the pathogen. Therefore the new compounds will seek to poison the vitamin-dependent enzymes as cofactors. (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)

BARRA, ANGELICA LUANA C.; ULLAH, NAJEEB; MORAO, LUANA G.; WRENGER, CARSTEN; BETZEL, CHRISTIAN; NASCIMENTO, ALESSANDRO S.. Structural Dynamics and Perspectives of Vitamin B6 Biosynthesis Enzymes in Plasmodium: Advances and Open Questions. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JUL 13 2021. (18/21213-6, 19/20219-3, 20/03983-9, 15/13684-0, 19/26428-3, 15/26722-8, 17/03966-4)