| Full text | |
| Author(s): Show less - |
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
|
| Affiliation: | [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 |
| 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 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 Opportunities: | 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 Opportunities: | Scholarships in Brazil - Post-Doctoral |
| 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 Oliveira |
| Support Opportunities: | 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 Opportunities: | Scholarships in Brazil - Doctorate |