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Structural and kinetical studies of the enzymes involved in the purine metabolism in Schistosoma mansoni

Grant number: 12/14223-9
Support type:Regular Research Grants
Duration: December 01, 2012 - November 30, 2014
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal researcher:Humberto D'Muniz Pereira
Grantee:Humberto D'Muniz Pereira
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

In the 70's Senft and coworkers published a series of articles demonstrating that S. mansoni was unable to incorporate both glycine and glucose in the purine ring indicating the lack of a "de novo" purine pathway in the parasite and highlighting its dependence on imported host's purine . Genes coding for all purine salvage enzymes were found in the S. mansoni genome. In S. mansoni, the purine salvage pathway is composed of 18 enzymes (five of them represent different isoforms of the same protein), in three different sub-pathways for conversion of adenosine to AMP or GMP. Given the importance of the purine salvage pathway for parasite metabolism, we are currently undertaking a systematic approach to investigating the structural biology and kinetics of the enzymes involved.It is expected that this knowledge will provide a more rational basis for target selection in the future. Specifically, this knowledge is necessary in order to understanding the ways in which the parasite could be selectively starved of resources, which could be used to develop new drugs and/or vaccines against this important human parasite. (AU)

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Scientific publications (11)
(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)
ROMANELLO, LARISSA; BALASCO SERRAO, VITOR HUGO; TORINI, JULIANA ROBERTA; BIRD, LOUISE E.; NETTLESHIP, JOANNE E.; RADA, HEATHER; REDDIVARI, YAMINI; OWENS, RAY J.; DEMARCO, RICARDO; BRANDAO-NETO, JOSE; et al. Structural and kinetic analysis of Schistosoma mansoni Adenylosuccinate Lyase (SmADSL). Molecular and Biochemical Parasitology, v. 214, p. 27-35, . (12/23730-1, 12/05532-8, 12/14223-9)
ROMANELLO, LARISSA; ZERAIK, ANA ELIZA; FERNANDES, ADRIANO DE FREITAS; TORINI, JULIANA ROBERTA; BIRD, LOUISE E.; NETTLESHIP, JOANNE E.; RADA, HEATHER; REDDIVARI, YAMINI; OWENS, RAY J.; SERRAO, VITOR HUGO BALASCO; et al. In vitro and in vivo characterization of the multiple isoforms of Schistosoma mansoni hypoxanthine-guanine phosphoribosyltransferases. Molecular and Biochemical Parasitology, v. 229, p. 24-34, . (12/05532-8, 12/14223-9, 13/20715-4, 12/23730-1)
DA SILVA NETO, ANTONIO MARINHO; TORINI DE SOUZA, JULIANA ROBERTA; ROMANELLO, LARISSA; CASSAGO, ALEXANDRE; BALASCO SERRAO, VITOR HUGO; DEMARCO, RICARDO; BRANDAO-NETO, JOSE; GARRATT, RICHARD CHARLES; PEREIRA, HUMBERTO D'MUNIZ. Analysis of two Schistosoma mansoni uridine phosphorylases isoforms suggests the emergence of a protein with a non-canonical function. Biochimie, v. 125, p. 12-22, . (12/14223-9)
TORINI, JULIANA ROBERTA; BRANDAO-NETO, JOSE; DEMARCO, RICARDO; PEREIRA, HUMBERTO D'MUNIZ. Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5 `-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway. PLoS Neglected Tropical Diseases, v. 10, n. 12, . (12/10213-9, 12/14223-9)
BALASCO SERRAO, VITOR HUGO; ROMANELLO, LARISSA; CASSAGO, ALEXANDRE; TORINI DE SOUZA, JULIANA ROBERTA; CHELESKI, JULIANA; DEMARCO, RICARDO; BRANDAO-NETO, JOSE; PEREIRA, HUMBERTO D'MUNIZ. Structure and kinetics assays of recombinant Schistosoma mansoni dihydrofolate reductase. Acta Tropica, v. 170, p. 190-196, . (12/23730-1, 12/14223-9)
TORINI, JULIANA ROBERTA; ROMANELLO, LARISSA; HELENO BATISTA, FERNANDA APARECIDA; BALASCO SERRAO, VITOR HUGO; FAHEEM, MUHAMMAD; ZERAIK, ANA ELIZA; BIRD, LOUISE; NETTLESHIP, JOANNE; REDDIVARI, YAMINI; OWENS, RAY; et al. The molecular structure of Schistosoma mansoni PNP isoform 2 provides insights into the nucleoside selectivity of PNPs. PLoS One, v. 13, n. 9, . (12/23730-1, 12/10213-9, 12/14223-9)
SCORTECCI, JESSICA FERNANDES; BALASCO SERRAO, VITOR HUGO; CHELESKI, JULIANA; TORINI, JULIANA ROBERTA; ROMANELLO, LARISSA; DEMARCO, RICARDO; PEREIRA, HUMBERTO D'MUNIZ. Spectroscopic and calorimetric assays reveal dependence on dCTP and two metals (Zn2+ + Mg2+) for enzymatic activity of Schistosoma mansoni deoxycytidylate (dCMP) deaminase. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1865, n. 11, A, p. 1326-1335, . (12/23730-1, 12/15777-8, 12/05532-8, 12/14223-9)
TORINI, JULIANA ROBERTA; FERNANDES, ADRIANO DE FREITAS; BALASCO SERRAO, VITOR HUGO; ROMANELLO, LARISSA; BIRD, LOUISE E.; NETTLESHIP, JOANNE E.; OWENS, RAYMOND J.; BRANDAO-NETO, JOSE; ZERAIK, ANA ELIZA; DEMARCO, RICARDO; et al. Characterization of a Schistosoma mansoni NDPK expressed in sexual and digestive organs. Molecular and Biochemical Parasitology, v. 231, . (12/14223-9, 13/20715-4, 12/10213-9, 12/23730-1)
BALASCO SERRAO, VITOR HUGO; TORINI DE SOUZA, JULIANA ROBERTA; ROMANELLO, LARISSA; PEREIRA, HUMBERTO D'MUNIZ. Schistosoma mansoni Purine and Pyrimidine Biosynthesis: Structures and Kinetic Experiments in the Search for the Best Therapeutic Target. CURRENT PHARMACEUTICAL DESIGN, v. 23, n. 45, p. 6967-6983, . (12/23730-1, 12/10213-9, 12/05532-8, 12/14223-9)
PINTO, ANDRESSA P. A.; PEREIRA, HUMBERTO M.; ZERAIK, ANA E.; CIOL, HELOISA; FERREIRA, FREDERICO M.; BRANDAO-NETO, JOSE; DEMARCO, RICARDO; NAVARRO, MARCOS V. A. S.; RISI, CRISTINA; GALKIN, VITOLD E.; et al. Filaments and fingers: Novel structural aspects of the single septin from Chlamydomonas reinhardtii. Journal of Biological Chemistry, v. 292, n. 26, p. 10899-10911, . (14/15546-1, 13/20715-4, 12/21259-0, 12/14223-9, 11/10152-7)
ZERAIK, ANA ELIZA; BALASCO SERRAO, VITOR HUGO; ROMANELLO, LARISSA; TORINI, JULIANA ROBERTA; CASSAGO, ALEXANDRE; DEMARCO, RICARDO; PEREIRA, HUMBERTO D'MUNIZ. Schistosoma mansoni displays an adenine phosphoribosyltransferase preferentially expressed in mature female gonads and vitelaria. Molecular and Biochemical Parasitology, v. 214, p. 82-86, . (12/23730-1, 12/10213-9, 13/20715-4, 12/14223-9, 12/05532-8)

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