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Identification of the nicotinamide mononucleotide adenylyltransferase of Trypanosoma cruzi
Niño, Carlos H; Forero-Baena, Nicolás; Contreras, Luis E; Sánchez-Lancheros, Diana; Figarella, Katherine; Ramírez, María H.
Afiliação
  • Niño, Carlos H; Universidad Nacional de Colombia. Facultad de Ciencias. Laboratorio de Investigaciones Básicas en Bioquímica. Bogotá. CO
  • Forero-Baena, Nicolás; Universidad Nacional de Colombia. Facultad de Ciencias. Laboratorio de Investigaciones Básicas en Bioquímica. Bogotá. CO
  • Contreras, Luis E; Universidad Nacional de Colombia. Facultad de Ciencias. Laboratorio de Investigaciones Básicas en Bioquímica. Bogotá. CO
  • Sánchez-Lancheros, Diana; Universidad Nacional de Colombia. Facultad de Ciencias. Laboratorio de Investigaciones Básicas en Bioquímica. Bogotá. CO
  • Figarella, Katherine; Universidad Nacional de Colombia. Facultad de Ciencias. Laboratorio de Investigaciones Básicas en Bioquímica. Bogotá. CO
  • Ramírez, María H; Universidad Nacional de Colombia. Facultad de Ciencias. Laboratorio de Investigaciones Básicas en Bioquímica. Bogotá. CO
Mem. Inst. Oswaldo Cruz ; 110(7): 890-897, Nov. 2015. tab, graf
Article em En | LILACS | ID: lil-764585
Biblioteca responsável: BR1.1
ABSTRACT
The intracellular parasite Trypanosomacruzi is the aetiological agent of Chagas disease, a public health concern with an increasing incidence rate. This increase is due, among other reasons, to the parasite’s drug resistance mechanisms, which require nicotinamide adenine dinucleotide (NAD+). Furthermore, this molecule is involved in metabolic and intracellular signalling processes necessary for the survival of T. cruzithroughout its life cycle. NAD+biosynthesis is performed by de novo and salvage pathways, which converge on the step that is catalysed by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT) (enzyme commission number 2.7.7.1). The identification of the NMNAT of T. cruziis important for the development of future therapeutic strategies to treat Chagas disease. In this study, a hypothetical open reading frame (ORF) for NMNAT was identified in the genome of T. cruzi.The corresponding putative protein was analysed by simulating structural models. The ORF was amplified from genomic DNA by polymerase chain reaction and was further used for the construction of a corresponding recombinant expression vector. The expressed recombinant protein was partially purified and its activity was evaluated using enzymatic assays. These results comprise the first identification of an NMNAT in T. cruziusing bioinformatics and experimental tools and hence represent the first step to understanding NAD+ metabolism in these parasites.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: LILACS Assunto principal: Trypanosoma cruzi / Nicotinamida-Nucleotídeo Adenililtransferase Tipo de estudo: Diagnostic_studies Idioma: En Revista: Mem. Inst. Oswaldo Cruz Ano de publicação: 2015 Tipo de documento: Article / Project document

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: LILACS Assunto principal: Trypanosoma cruzi / Nicotinamida-Nucleotídeo Adenililtransferase Tipo de estudo: Diagnostic_studies Idioma: En Revista: Mem. Inst. Oswaldo Cruz Ano de publicação: 2015 Tipo de documento: Article / Project document