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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Biochemical Parasitology; v. 231, JUL 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 12/14223-9 - Estudos estruturais e cinéticos das enzimas da via de salvação de purina de Schistosoma mansoni
• Beneficiário: Humberto D'Muniz Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/20715-4 - Estudo da correlação entre a dinâmica de septinas e a homeostase de Ca2+ em células musculares de Schistosoma mansoni
• Beneficiário: Ana Eliza Zeraik
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/10213-9 - Determinação estrutural e funcional das enzimas Metiltioadenosina Fosforilase, Purina Nucleosídeo Fosforilase isoforma 2 e das enzimas participantes da produção de GTP da via de salvação de purinas em Schistosoma mansoni.
• Beneficiário: Juliana Roberta Torini de Souza Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/23730-1 - Caracterização das interações macromoleculares das proteínas envolvidas na síntese de selenocisteínas em escherichia coli
• Beneficiário: Vitor Hugo Balasco Serrão
• Modalidade de apoio: Bolsas no Brasil - Doutorado