Structural and kinetic studies of adenosine kinase, hypoxanthine-guanine phosphoribosyltransferase, Adenilsuccinate Synthetase and Adenilsuccinato Lyase enzymes from Schistosoma mansoni

• Grant number: 12/05532-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2012
• End date: May 31, 2016
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Humberto D'Muniz Pereira
• Grantee: Larissa Romanello
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Schistosoma mansoni, parasite responsible for schistosomiasis, a disease that affects about 300 million people worldwide, lacks the synthetic pathway of purines, depending entirely on the way to salvation for their supply of purine bases of these. The enzyme adenosine kinase (AK), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenilosuccinato synthase (ADSS) and adenilosuccinato lyase (ADSL) are enzymes of this pathway. AK is directly responsible for phosphorylation of adenosine to adenosine monophosphate (AMP), HGPRT catalyzes the phosphorybosilation reversible guanine and hypoxanthine to IMP or GMP, ADSS catalyzes the conversion of IMP combined with aspartate at adenilsuccinato, ADSL hydrolyzed in adenilsuccinato fumarate and AMP . This route has been cited as a potential target for drug development against schistosomiasis. The main objectives of this project are: amplification and cDNA cloning, expression, purification and biochemical characterization of enzymes, to determine the catalytic constants for the various enzyme substrates and three-dimensional structure by X-ray diffraction. This work is part of a larger project aimed at getting all the structures of enzymes involved in purine pathway of salvation of Schistosoma mansoni.

Scientific publications

(7)

(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)

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, NOV 2017. (12/05532-8, 12/23730-1, 12/14223-9, 12/15777-8)

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)

CAGNAZZO, TULIO DI ORLANDO; NOGUEIRA, CAMILA TITA; DE CASTRO, CYNTHIA APARECIDA; NERIS, DEBORA MEIRA; FATTORI, ANA CAROLINA MARAGNO; CORREIA, RICARDO DE OLIVEIRA; ALBUQUERQUE, YULLI ROXENNE; FRAGELLI, BRUNA DIAS DE LIMA; MENDES, TIAGO MANUEL FERNANDES; ALLEGRETTI, SILMARA MARQUES; et al. Investigating Immunization With Nucleotide Enzymes ofSchistosoma mansoni: Nucleoside Diphosphate Kinase and Adenylosuccinate Lyase as New Antigenic Targets Against Schistosomiasis. FRONTIERS IN IMMUNOLOGY, v. 11, p. 11-pg., 2020-09-23. (12/14223-9, 12/05532-8, 14/07331-5)

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, APR 2019. (12/05532-8, 12/14223-9, 13/20715-4, 12/23730-1)

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, JUN 2017. (12/05532-8, 12/14223-9, 12/23730-1)

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, p. 10-pg., 2017-11-01. (12/05532-8, 12/14223-9, 12/15777-8, 12/23730-1)

Academic Publications

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

ROMANELLO, Larissa. Studies of adenosine kinase isoform 1, hypoxanthine-guanine phosphoribosyltransferase isoforms 1, 2 and 3, adenylosuccinate lyase, adenylosuccinate synthetase enzymes from Schistosoma mansoni. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.