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Structural and functional characterization of Trypanosoma cruzi fumarate hydratase isoforms

Grant number: 08/11644-8
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): May 01, 2009
Effective date (End): January 31, 2014
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Maria Cristina Nonato
Grantee:Ricardo Augusto Pereira de Pádua
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Chagas Disease, caused by a protozoan flagellate parasite called Trypanosoma cruzi, is a serious burden to public health, affecting millions of people in Latin America. Considered as a neglected tropical disease by WHO, Chagas Disease is transmitted to humans by triatomine insects, through blood transfusion, congenitally and by ingestion of contaminated food. Unfortunately, the available drugs benzinidazole and nifurtimox are excessively toxic which implies an urgent need for the development of new therapies against Chagas Disease. Our work focuses the identification and characterization of potential macromolecular targets for the development of effective chemotherapy. In this context, it is our interest to characterize T. cruzi fumarases in order to evaluate these enzymes as potential drug targets. This project focuses in the generation o T. cruzi fumarase knockout cell lines, fumarases sub-cellular localization in these parasites, as well as the cloning, expression, purification and structural characterization of T. cruzi fumarases. (AU)

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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)
PADUA, RICARDO A. P.; TOMALERI, GIOVANI P.; REIS, RENATA A. G.; DAVID, JULIANA S.; SILVA, VALERIA C.; PINHEIRO, MATHEUS P.; NONATO, MARIA CRISTINA. ThermoFMN - a thermofluor assay developed for ligand-screening as an alternative strategy for drug discovery. Journal of the Brazilian Chemical Society, v. 25, n. 10, p. 1864+, . (11/23504-9, 07/08703-0, 08/11644-8, 11/14269-6, 12/25075-0)
PEREIRA DE PADUA, RICARDO AUGUSTO; NONATO, MARIA CRISTINA. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of recombinant human fumarase. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 70, n. 1, p. 120-122, . (08/08262-6, 08/11644-8)
DE PADUA, RICARDO A. P.; KIA, ALI MARTIN; COSTA-FILHO, ANTONIO J.; WILKINSON, SHANE R.; NONATO, M. CRISTINA. Characterisation of the fumarate hydratase repertoire in Trypanosoma cruzi. International Journal of Biological Macromolecules, v. 102, p. 42-51, . (08/08262-6, 15/18390-5, 08/11644-8)

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