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Identification and functional characterization of a bacterial homologue of Zeta toxin in Leishmania donovani

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Zeta‐toxin is a cognate toxin of epsilon antitoxin of prokaryotic Type II toxin‐antitoxin system (TA) and play an important role in cell death. An orthologue of bacterial‐zeta‐toxin (BzT) was identified… Click to show full abstract

Zeta‐toxin is a cognate toxin of epsilon antitoxin of prokaryotic Type II toxin‐antitoxin system (TA) and play an important role in cell death. An orthologue of bacterial‐zeta‐toxin (BzT) was identified in Leishmania donovani with similar structural and functional features. Leishmania zeta‐toxin (named Ld_ζ1) harboring similar UNAG and ATP‐binding pockets showed UNAG kinase and ATP‐binding activity. An active Ld_ζ1 was found to express in infective extracellular promastigotes stage of L. donovani and episomal overexpression of an active Ld_ζ1domain‐triggered cell death. This study demonstrates the presence of prokaryotic‐like‐zeta‐toxin in eukaryotic parasite Leishmania and its association with cell death. Conceivably, phosphorylated UNAG or analogues, the biochemical mimics of zeta‐toxin function mediating cell death can act as a novel anti‐leishmanial chemotherapeutics.

Keywords: leishmania donovani; zeta toxin; toxin; cell death

Journal Title: FEBS Letters
Year Published: 2019

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