Structure determination of fumarate hydratase isoforms from Leishmania major

• Grant number: 11/19674-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 19, 2012
• End date: February 18, 2013
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Maria Cristina Nonato
• Grantee: Patrícia Rosa Feliciano
• Supervisor: Catherine L. Drennan
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Massachusetts Institute of Technology (MIT), United States
• Associated to the scholarship: 09/10454-3 - Studies of the correlation between structure and function of the enzyme fumarate hydratase in Leishmania major, BP.DR

Abstract

Fumarate hydratases catalyze the stereospecific reversible hydration of fumarate to S-malate. This project aims to determine the 3-dimensional structure of two fumarate hydratases from Leishmania major by single crystal x-ray diffraction. Leishmania is a parasite that causes Leishmaniases, classified as neglected tropical deseases and threatening 350 million people around the world. Recent studies in trypanosomatids, using Trypanosoma brucei as a model, suggest that fumarate hydratase may be exploited as a potential target for the development of anti-trypanosomatid drugs. Structural studies, proposed in this work, associated to our previous kinetic and cell localization studies will be used to further to establish the structure-function relationship of both fumarate hydratase enzymes in Leishmania major. The results obtained during the development of this project will provide valuable information for the development of specific inhibitors as an important tool in the fight against Leishmaniasis. (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)

FELICIANO, PATRICIA R.; DRENNAN, CATHERINE L.; CRISTINA NONATO, M.. Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold. Proceedings of the National Academy of Sciences of the United States of America, v. 113, n. 35, p. 9804-9809, AUG 30 2016. (09/10454-3, 11/19674-6, 08/08262-6)

FELICIANO, PATRICIA R.; DRENNAN, CATHERINE L.; CRISTINA NONATO, M.. Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 113, n. 35, p. 6-pg., 2016-08-30. (08/08262-6, 11/19674-6, 09/10454-3)