A novel stage-specific glycosomal nucleoside diphosphate kinase from Trypanosoma cruzi

CAMARA, MARIA DE LOS MILAGROS; BOUVIER, LEON; REIGADA, CHANTAL; DI GIROLAMO, FABIO; SAYE, MELISA; PEREIRA, CA

FOLIA PARASITOLOGICA

FOLIA PARASITOLOGICA

Año: 2017

0015-5683

Nucleoside diphosphate kinases are key enzymes involved in the intracellular27 nucleotide maintenance in all living organisms, especially in trypanosomatids which are28 unable to synthesize purines de novo. Four putative NDPK isoforms were identified in the29 Trypanosoma cruzi genome but only two of them were characterized so far. In this work, we30 studied a novel isoform from T. cruzi called TcNDPK3. This enzyme presents an atypical N31terminal extension similar to the DM10 domains. In T. cruzi, DM10 sequences targeted other32 NDPK isoform (TcNDPK2) to the cytoskeleton; however, TcNDPK3 was localized in33 glycosomes despite lacking a typical peroxisomal targeting signal. In addition, TcNDPK334 was found only in the bloodstream trypomastigotes where glycolytic enzymes are very35 abundant. However, TcNDPK3 mRNA was also detected at lower levels in amastigotes36 suggesting regulation at protein and mRNA level. Finally, 33 TcNDPK3 gene orthologs were37 identified in the available kinetoplastid genomes. The characterization of new glycosomal38 enzymes provides novel targets for drug development to use in therapies of trypanosomatid39 associated diseases.