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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Characterization of a Schistosoma mansoni NDPK expressed in sexual and digestive organs

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Torini, Juliana Roberta [1] ; Fernandes, Adriano de Freitas [1] ; Balasco Serrao, Vitor Hugo [1, 2] ; Romanello, Larissa [1] ; Bird, Louise E. [3] ; Nettleship, Joanne E. [3] ; Owens, Raymond J. [4] ; Brandao-Neto, Jose [4] ; Zeraik, Ana Eliza [1] ; DeMarco, Ricardo [1] ; Pereira, Humberto D'Muniz [1]
Total Authors: 11
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Lab Biol Estrutural, BR-13563120 Sao Carlos, SP - Brazil
[2] Univ Toronto, Dept Med Pathobiol, 1 Kings Coll Circle, Toronto, ON M5S 1A8 - Canada
[3] Rutherford Appleton Lab, Res Complex Harwell, OPPF UK, Oxford OX11 0FA - England
[4] Diamond Light Source, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon - England
Total Affiliations: 4
Document type: Journal article
Source: Molecular and Biochemical Parasitology; v. 231, JUL 2019.
Web of Science Citations: 0

Nucleoside diphosphate kinases (NDPKs) are crucial to keep the high triphosphate nucleotide levels in the biological process. The enzymatic mechanism has been extensively described; however, the structural characteristics and kinetic parameters have never been fully determined. In Schistosoma mansoni, NDPK (SmNDPK) is directly involved in the pyrimidine and purine salvage pathways, being essential for nucleotide metabolism. The SmNDPK enzymatic activity is the highest of the known purine metabolisms when compared to the mammalian NDPKs, suggesting the importance of this enzyme in the worm metabolism. Here, we report the recombinant expression of SmNDPK that resulted in 1.7 and 1.9 angstrom apo-form structure in different space-groups, as well as the 2.1 angstrom SmNDPK.ADP complex. The binding and kinetic assays reveal the ATP-dependence for enzyme activation. Moreover, in situ hybridization showed that SmNDPK transcripts are found in reproductive organs and in the esophagus gland of adult worms, which can be intrinsically related with the oviposition and digestive processes. These results will help us fully understand the crucial participation of this enzyme in Schistosoma mansoni and its importance for the pathology of the disease. (AU)

FAPESP's process: 12/14223-9 - Structural and kinetical studies of the enzymes involved in the purine metabolism in Schistosoma mansoni
Grantee:Humberto D'Muniz Pereira
Support type: Regular Research Grants
FAPESP's process: 13/20715-4 - Studies of the correlation between septin dynamics and Ca2+ homeostasis in muscular cells from Schistosoma mansoni
Grantee:Ana Eliza Zeraik
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/10213-9 - 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
Grantee:Juliana Roberta Torini de Souza
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 12/23730-1 - Characterization of macromolecular interactions of proteins involved in the selenocysteine synthesis from Escherichia coli
Grantee:Vitor Hugo Balasco Serrão
Support type: Scholarships in Brazil - Doctorate