Structural and functional studies of Purine nucleoside phosphorylase isoform 2, Methylthioadenosine phosphorylase and participants enzymes of GTP production from purine salvage pathway from Schistosoma mansoni.

• Grant number: 12/10213-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2012
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Humberto D'Muniz Pereira
• Grantee: Juliana Roberta Torini de Souza Oliveira
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

The parasitic diseases, are the biggest cause of the death on progress countries, therefore it don't receive any attention by pharmaceutical industry for development of therapeutics processes. The schistosomiasis affects approximately 207 million people worldwide and 6 million on Brazil. The parasite Schistosoma mansoni does not possess "de novo" pathway for purine bases biosynthesis and depends entirely on salvage pathways for its purine requirement. Thus this pathway can be identified as a potential target to be explored. The Inosine monophosphate dehydrogenase (IMPDH), GMP-syntetase (GMPS), Guanylate kinase (GK), Nucleoside diphosphate kinase (NDPK), Purine nucleoside phosphorylase isoform 2 (PNP2) and Methylthioadenosine phosphorylase (MTAP) enzymes are involved in this pathway. The IMPDH is responsible for converting inosine monophosphate into xhantine monophosphate, the GMPS for converting xhantine monophosphate into guanosine monophosphate, the NDPK for converting nucleotides diphosphate into correspondent nucleotides triphosphate, the PNP2 for reversible phosphorolysis of purines nucleosides and the MTAP for converting adenosine into adenine. The objectives this study are clone, express and purify the IMPDH, GMPS, GK e PNP2 enzymes for structural and functional determination, beyond accurate investigation of the catalytic mechanisms from MTAP enzyme. This project is inserted on larger project on progress, which purpose is to obtain the tridimensional structure and catalytic constants of the all enzymes from the purine salvation pathway from Schistosoma mansoni.

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)

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, JUL 2019. (12/14223-9, 13/20715-4, 12/10213-9, 12/23730-1)

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, JUN 2017. (12/10213-9, 12/05532-8, 12/14223-9, 13/20715-4, 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, 2017. (12/05532-8, 12/14223-9, 12/10213-9, 12/23730-1)

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, SEP 7 2018. (12/14223-9, 12/10213-9, 12/23730-1)

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, p. 25-pg., 2016-12-01. (12/10213-9, 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, DEC 2016. (12/10213-9, 12/14223-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

OLIVEIRA, Juliana Roberta Torini de Souza. Structural and functional characterization of two Nucleoside Phosphorylase from Schistosoma mansoni.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.