National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases

• Grant number: 08/57910-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 2009
• End date: June 30, 2015
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Agreement: CNPq - INCTs
• Principal Investigator: Richard Charles Garratt
• Grantee: Richard Charles Garratt
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant(s): 13/02383-4 - Visit to the Center for Structural Molecular Biotechnology of the IFSC and presentation at the annual meeting of the Brazilian Society for Biochemistry and Molecular Biology, AV.EXT; 12/09533-9 - International Congress on Natural Products Research, AR.EXT
• Associated scholarship(s): 14/16005-4 - Characterization of the molecular interactions within selenocysteine synthesis pathway proteins, BP.IC; 13/26996-5 - Molecular cloning and expression of Trypanosoma brucei U5-200K protein for tandem purification experiments, BP.IC; 13/27013-5 - Biophysical characterization of the U5-200K protein involved in Trypanosoma brucei pre-mRNA processing, BP.IC; + associated scholarships 13/15935-5 - Biochemical and structural investigation of Naegleria gruberi selenophosphate sintetase enzyme, BP.MS; 12/23730-1 - Characterization of macromolecular interactions of proteins involved in the selenocysteine synthesis from Escherichia coli, BP.DR; 12/04281-1 - Metabolic investigation in trypanosomatids using steady-state free precession (SSFP) nuclear magnetic resonance, BP.PD; 11/24017-4 - Study of selenium metabolism in primitive eukaryotes, BP.PD; 11/06087-5 - Identification and characterization of replication origins in Trypanosoma and Leishmania, BP.PD; 10/12953-4 - Structural determination of the C-terminal domains of septins SEPT2 and SEPT4 and protein interaction with alpha-synuclein by NMR, BP.PD; 08/01220-6 - Isoprenoid biosynthetic study in Smallanthus sonchifolius and in the endophytic fungus Nigrospora sphaerica associated to the LC-MS monitoring of the sesquiterpene lactone enidrin production in endophytic cultures, BP.PD - associated scholarships

Abstract

The National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases (INBEQMeDI) is a joint initiative resulting from existing collaborative research projects focused at the development of structural and biological studies on specific molecular targets in microorganisms associated with neglected tropical infectious diseases, aiming at the development of new drug candidates for the treatment of the endemic diseases Leishmaniasis, Schistosomiasis, Chagas' disease and malaria. This proposal is fostered by our previous successful initiative of the CEPID-FAPESP Center for Structural Molecular Biotechnology, which, for the past 8 years, has conducted frontline research projects in structural biotechnology and medicinal chemistry, including patent development, technological transfer and the dissemination of science through several programs dedicated to high-school students and teachers, as well as the population in general. Another fundamental basis for this proposal is the fact that we have been recently selected by World Health Organization, through its Tropical Diseases Research Program (TDR) as a World Reference Center for Medicinal Chemistry in Chagas Disease. This proposal is lead by the Center for Structural Molecular Biotechnology of the Institute of Physics of São Carlos (IFSC), University of São Paulo (USP), the first, most traditional and prestigious research group in Protein Crystallography and Structure-Based Drug Design in this country. In addition to this lead group, we are proposing, as associate research groups: 1) the Laboratory of Natural Products and Organic Synthesis of the Department of Chemistry, Federal University of São Carlos (DQ-UFSCar); Four other research groups on parasitology and medicinal chemistry of the University of São Paulo; 2) the Laboratory for the Study of the Molecular Bases of Signal Transduction in the Malaria Parasite, of the Department of General Physiology, Institute of Biosciences (IB-USP); 3) the Laboratory of Dr. A.Silber of the Department of Parasitology, Institute of Biomedical Sciences (ICB-USP); 4) the Laboratory of Prof. Angela K. Cruz, of the Department of Cell and Molecular Biology of Pathogenic Agents, Medicai Faculty of Ribeirao Preto (FMRP-USP); The Laboratory of Chemical and Biological Prospection in Funghi and Actinobacter, of the Faculty of Pharmaceutical Sciences of Ribeirão Preto (FCFRP-USP). Additionally, the INBEQMeDI includes two young investigators as Associate Laboratories, Dr. Jorge Iulek, a protein crystallographer based at the Universidade Estadual de Ponta Grossa, Paraná, and Juliana Lopes Rangel Fietto, a molecular biologist working at the Universidade Federal de Viçosa, Departamento de Bioquímica e Biologia Molecular. The major goal of this Center is to perform both applied and basic research as well as technological development and science education in neglected tropical infectious diseases, which depend on Structure Based Molecular Design, specifically in the rational design of new structure-based drugs and vaccines. In order to achieve this goal, the INBEQMeDI promotes an integrated multidisciplinary approach including the application of the techniques of Molecular Biology, Biochemistry, Structural Biology (Protein Crystallography, Multidimensional NMR, Spectroscopies, Molecular Modeling and Bioinformatics), Medicinal Chemistry based on both Synthetic and Natural Products Chemistry, Molecular Immunology, Cell Biology and Pharmacology. The projects undertaken by the INBEQMeDI are selected on the basis of their potential as targets for chemotherapy in tropical diseases. Integration and collaboration with the private sector is always sought, particularly with pharmaceutical and biotechnology companies and research institutes within the health sector. (AU)

Scientific publications

(14)

(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)

PENTEADO, R. F.; MARTINI, V. P.; IULEK, J.. Crystallization and Crystallographic Analyses of Triosephosphate Isomerase from Naegleria gruberi. REVISTA VIRTUAL DE QUIMICA, v. 8, n. 6, p. 1835-1841, 2016. (08/57910-0)

BOREIKO, S.; SILVA, M.; IULEK, J.. Crystallization and X Ray Diffraction Data Analyses of the Enzyme Urocanate Hydratase from Trypanosoma cruzi. REVISTA VIRTUAL DE QUIMICA, v. 8, n. 3, p. 678-686, 2016. (08/57910-0)

SILVA, IVAN R.; SERRAO, VITOR H. B.; MANZINE, LIVIA R.; FAIM, LIVIA M.; DA SILVA, MARCO T. A.; MAKKI, RAPHAELA; SAIDEMBERG, DANIEL M.; CORNELIO, MARINONIO L.; PALMA, MARRIO S.; THIEMANN, OTAVIO H.. Formation of a Ternary Complex for Selenocysteine Biosynthesis in Bacteria. Journal of Biological Chemistry, v. 290, n. 49, p. 29178-U103, DEC 4 2015. (10/04429-3, 08/57910-0)

BALASCO SERRAO, VITOR HUGO; ALESSANDRO, FERNANDO; ARMINI CALDAS, VICTOR EMANOEL; MARCAL, RAFAELA LEITE; PEREIRA, HUMBERTO D'MUNIZ; THIEMANN, OTAVIO HENRIQUE; GARRATT, RICHARD CHARLES. Promiscuous interactions of human septins: The GTP binding domain of SEPT7 forms filaments within the crystal. FEBS Letters, v. 585, n. 24, p. 3868-3873, DEC 15 2011. (08/57910-0, 98/14138-2)

BASSO, LUIS G. M.; RODRIGUES, RENATA Z.; NAAL, ROSE M. Z. G.; COSTA-FILHO, ANTONIO J.. Effects of the antimalarial drug primaquine on the dynamic structure of lipid model membranes. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1808, n. 1, p. 55-64, JAN 2011. (08/57910-0)

MACEDO, JOCI N. A.; VALADARES, NAPOLEAO F.; MARQUES, IVO A.; FERREIRA, FREDERICO M.; DAMALIO, JULIO C. P.; PEREIRA, HUMBERTO M.; GARRATT, RICHARD C.; ARAUJO, ANA P. U.. The structure and properties of septin 3: a possible missing link in septin filament formation. Biochemical Journal, v. 450, n. 1, p. 95-105, FEB 15 2013. (06/57573-9, 08/57910-0, 98/14138-2)

ALVES DA SILVA, MARCO TULIO; ROSA E SILVA, IVAN; FAIM, LIVIA MARIA; BELLINI, NATALIA KARLA; PEREIRA, MURILO LEAO; LIMA, ANA LAURA; LEANDRO DE JESUS, TERESA CRISTINA; COSTA, FERNANDA CRISTINA; WATANABE, TATIANA FARIA; PEREIRA, HUMBERTO D'MUNIZ; et al. Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase. PLoS Neglected Tropical Diseases, v. 14, n. 10, OCT 2020. (08/57910-0, 11/24017-4, 10/04429-3, 13/02848-7, 11/06087-5, 07/06591-0)

BOREIKO, SHEILA; SILVA, MARCIO; MELO, RAISSA DE F. P.; SILBER, ARIEL M.; IULEK, JORGE. Structure of Urocanate Hydratase from the protozoan Trypanosoma cruzi. International Journal of Biological Macromolecules, v. 146, p. 716-724, MAR 1 2020. (08/57910-0, 16/06034-2)

MANSOR BASSO, LUIS GUILHERME; ZERAIK, ANA ELIZA; FELIZATTI, ANA PAULA; COSTA-FILHO, ANTONIO JOSE. Membranotropic and biological activities of the membrane fusion peptides from SARS-CoV spike glycoprotein: The importance of the complete internal fusion peptide domain. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1863, n. 11, NOV 1 2021. (08/57910-0, 15/50366-7, 14/00206-0, 15/18390-5)

LEANDRO DE JESUS, TERESA CRISTINA; NUNES, VINICIUS SANTANA; LOPES, MARIANA DE CAMARGO; MARTIL, DAIANA EVELIN; IWAI, LEO KEI; MORETTI, NILMAR SILVIO; MACHADO, FABRICIO CASTRO; DE LIMA-STEIN, MARIANA L.; THIEMANN, OTAVIO HENRIQUE; ELIAS, MARIA CAROLINA; et al. Chromatin Proteomics Reveals Variable Histone Modifications during the Life Cycle of Trypanosoma cruzi. JOURNAL OF PROTEOME RESEARCH, v. 15, n. 6, p. 2039-2051, JUN 2016. (13/07467-1, 14/03714-7, 08/57910-0, 15/04867-4, 11/06087-5, 11/51973-3, 11/22619-7, 14/01577-2)

ZERAIK, ANA E.; PEREIRA, HUMBERTO M.; SANTOS, YURI V.; BRANDAO-NETO, JOSE; SPOERNER, MICHAEL; SANTOS, MAIARA S.; COLNAGO, LUIZ A.; GARRATT, RICHARD C.; ARAUJO, ANA P. U.; DEMARCO, RICARDO. Crystal Structure of a Schistosoma mansoni Septin Reveals the Phenomenon of Strand Slippage in Septins Dependent on the Nature of the Bound Nucleotide. Journal of Biological Chemistry, v. 289, n. 11, p. 7799-7811, MAR 14 2014. (08/57910-0)

BASSO, LUIS G. M.; VICENTE, EDUARDO F.; CRUSCA, JR., EDSON; CILLI, EDUARDO M.; COSTA-FILHO, ANTONIO J.. SARS-CoV fusion peptides induce membrane surface ordering and curvature. SCIENTIFIC REPORTS, v. 6, NOV 28 2016. (10/12953-4, 09/10997-7, 08/57910-0, 14/00206-0, 15/18390-5)

LEITE, NEY RIBEIRO; KROGH, RENATA; XU, WEI; ISHIDA, YUKO; IULEK, JORGE; LEAL, WALTER S.; OLIVA, GLAUCIUS. Structure of an Odorant-Binding Protein from the Mosquito Aedes aegypti Suggests a Binding Pocket Covered by a pH-Sensitive ``Lid{''}. PLoS One, v. 4, n. 11, NOV 26 2009. (08/57910-0)

MACEDO, JOCI N. A.; VALADARES, NAPOLEAO F.; MARQUES, IVO A.; FERREIRA, FREDERICO M.; DAMALIO, JULIO C. P.; PEREIRA, HUMBERTO M.; GARRATT, RICHARD C.; ARAUJO, ANA P. U.. The structure and properties of septin 3: a possible missing link in septin filament formation. Biochemical Journal, v. 450, p. 11-pg., 2013-02-15. (06/57573-9, 98/14138-2, 08/57910-0)