Structural and functional characterization of proteins envolved in the virulence of the protozoan parasite Leishmania major

• Grant number: 07/06755-2
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2008
• End date: April 30, 2010
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Arthur Henrique Cavalcante de Oliveira
• Grantee: Arthur Henrique Cavalcante de Oliveira
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The study of the structure and function of Leishmania proteins presents an opportunity to understand the molecular basis of the host/parasite interaction and discovery new targets for development of therapies against the parasite. The poposed project has the objective to investigate the structural and functional aspects of Leishmania major proteins that were previously identified in a subproteomic study of total extract of vesicles of Leishmania species. The strategy is based on the convergence of structural biology and functional analysis for the elucidation of the functional relevance of these proteins to the biology of the parasite, with particular enphasis on pathogenic factors. Two targets (NDK, Nucleoside Diphosphate Kinase and MIF, Macrophage Migration Inhibitory Factor) have been selected from the subproteome study wich present immunomodulatory functions in other pathogenic organisms. These two selected targets for this project have not been characterized in trypanosomatid parasites. The project will be developed by means of two approachs. The first is directed forwards structural and enzymatic characterization of the two targets , spectroscopy studies and resolution of the 3D structure by X-ray. The second approach will be directed forwords the functional characterization of proteins in the L. major (virulent lines) by immunolocalization, interaction of proteins with macrophages, constitutive superexpression of the genes in the promastigote forms of L. major and virulence analysis of the parasite transfected forms.The approval of this project will allow the establishement of the Laboratory of Biochemistry of Parasite Proteins in the FFCLRP-USP, which will be the first laboratory to focus on parasite proteins within the FFCLRP-USP, and will strengthen a network of biochemistry and parasitology laboratories both within the department and between other units on the campus of USP-Ribeirão Preto. (AU)

Scientific publications

(6)

(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)

COSTA TONOLI, CELISA CALDANA; VIEIRA, PLINIO SALMAZO; WARD, RICHARD JOHN; ARNI, RAGHUVIR KRISHNASWAMY; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; MURAKAMI, MARIO TYAGO. Production, purification, crystallization and preliminary X-ray diffraction studies of the nucleoside diphosphate kinase b from Leishmania major. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 65, n. 11, p. 1116-1119, NOV 2009. (07/06755-2)

VIEIRA, PLINIO SALMAZO; DE GIUSEPPE, PRISCILA OLIVEIRA; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; MURAKAMI, MARIO TYAGO. The role of the C-terminus and Kpn loop in the quaternary structure stability of nucleoside diphosphate kinase from Leishmania parasites. Journal of Structural Biology, v. 192, n. 3, p. 336-341, DEC 2015. (11/20569-2, 10/03761-4, 07/06755-2, 11/24178-8, 10/51730-0)

VIEIRA, PLINIO SALMAZO; CAMPOS BRASIL SOUZA, TATIANA DE ARRUDA; HONORATO, RODRIGO VARGAS; ZANPHORLIN, LETICIA MARIA; SEVERIANO, KELVEN ULISSES; ROCCO, SILVANA APARECIDA; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; CORDEIRO, ARTUR TORRES; LOPES OLIVEIRA, PAULO SERGIO; DE GIUSEPPE, PRISCILA OLIVEIRA; et al. Pyrrole-indolinone SU11652 targets the nucleoside diphosphate kinase from Leishmania parasites. Biochemical and Biophysical Research Communications, v. 488, n. 3, p. 461-465, JUL 1 2017. (11/20569-2, 10/03761-4, 07/06755-2, 11/24178-8, 10/51730-0)

COSTA TONOLI, CELISA CALDANA; VIEIRA, PLINIO SALMAZO; WARD, RICHARD JOHN; ARNI, RAGHUVIR KRISHNASWAMY; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; MURAKAMI, MARIO TYAGO. Production, purification, crystallization and preliminary X-ray diffraction studies of the nucleoside diphosphate kinase b from Leishmania major. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 65, p. 4-pg., 2009-11-01. (07/06755-2)

VIEIRA, PLINIO S.; DE JESUS SANTOS, ANA P.; DE OLIVEIRA, ARTHUR H. C.. Biophysical Characterization of the Nucleoside Diphosphate Kinase of Leishmania major and Effect of the P95S Mutation. PROTEIN AND PEPTIDE LETTERS, v. 23, n. 2, p. 99-106, 2016. (11/20569-2, 07/06755-2, 10/03761-4)

DE OLIVEIRA, ARTHUR H. C.; FERREIRA, TATIANA L.; WARD, RICHARD J.. Reduced pH induces an inactive non-native conformation of the monomeric bothropstoxin-I (Lys49-PLA(2)). Toxicon, v. 54, n. 3, p. 373-378, SEP 1 2009. (07/06755-2)