Advanced search
Start date
Betweenand

Production of mutant arginase enzyme from Leishmania (Leishmania) amazonensis for crystallization study

Grant number: 14/10521-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2014
Effective date (End): February 28, 2015
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Edson Roberto da Silva
Grantee:Caroline Comanini Augusto
Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil

Abstract

The arginase enzyme is the first enzyme in the polyamine synthesis pathway in Leishmania. It converts L-arginine into L-ornithine and urea. The ornithine decarboxylase (ODC) produces putrescine by L-ornithine decarboxylation. The putrescine is used as a substrate in the polyamines biosynthesis such as spermidine and spermine. Spermidine is a substrate of the trypanothione synthase that condensing this compound with glutathione generating trypanothione. Trypanothione is used by trypanothione reductase enzyme in the reduction of ROS (reactive oxygen species) produced in the mitochondria of the parasite and host macrophage. Trypanothione is also used in neutralizing NO (nitric oxide). We have recently described the inhibition of arginase of Leishmania (Leishmania) amazonensis by flavonoids, flavanoids and anthocyanidins. These compounds are competitive, uncompetitive, non-competitive and mixed inhibitors of the arginase enzyme. Study of the interaction of these molecules through crystallography can provide data for the rational drug design based on natural compound. Thus, we propose in this project the construction of mutants of arginase from L. (L.) amazonensis in order to stabilize the enzyme for crystallization studies with natural inhibitors.

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.