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

DOI: 10.1016/j.molbiopara.2019.111187 DOI Help

Authors: Juliana Roverta Torini (Universidade de São Paulo) , Adriano De Freitas Fernandes (Universidade de São Paulo) , Vitor Hugo Balasco Serrao (Universidade de São Paulo; University of Toronto) , Larissa Romanello (Universidade de São Paulo) , Louise Bird (OPPF-UK, Research Complex at Harwell) , Joanne E. Nettleship (OPPF-UK, Research Complex at Harwell) , Raymond J. Owens (OPPF-UK, Research Complex at Harwell) , Jose Brandao-Neto (Diamond Light Source) , Ana Eliza Zeraik (Universidade de São Paulo) , Ricardo Demarco (Universidade de São Paulo) , Humberto D'Muniz Pereira (Universidade de São Paulo)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular And Biochemical Parasitology , VOL 231

State: Published (Approved)
Published: July 2019
Diamond Proposal Number(s): 5073 , 14493

Abstract: 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 Å apo-form structure in different space-groups, as well as the 2.1 Å 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.

Journal Keywords: Crystallography; Isothermal titration calorimetry; NDPK; Schistosoma mansoni

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 21/05/2019 14:54

Discipline Tags:

Infectious Diseases Health & Wellbeing Biochemistry Catalysis Chemistry Structural biology Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)