Polyamine-trypanothione pathway: an update
Andrea Ilari1,2, Annarita Fiorillo1,3, Ilaria Genovese3
1CNR - National Research Council of Italy, Institute of Molecular Biology & Pathology, c/o Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, P.le Aldo Moro 5, 00185 - Rome, Italy.
Abstract:
In trypanosomatids, polyamine and trypanothione pathways can be considered as a whole unique metabolism, where most enzymes are essential for parasitic survival and infectivity. Leishmania parasites and all the other members of the Trypanosomatids family depend on polyamines for growth and survival: the enzymes involved in the synthesis and utilization of spermidine and trypanothione, i.e., arginase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermidine synthase and in particular trypanothione synthetase-amidase, trypanothione reductase and tryparedoxin-dependent peroxidase are promising targets for drug development. This review deals with recent structure-based studies on these enzymes, aimed at the discovery of inhibitors of this pathway.
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