Kinetic analyses and inhibition studies reveal novel features in peptide deformylase 1 from Trypanosoma cruzi
2012
Rodrígues-Poveda, Carlos A. | Pérez-Moreno, Guiomar | Vidal, Antonio E. | Urbina, Julio A. | González-Pacanowska, Dolores | Ruiz-Pérez, Luis M.
In eubacteria and eukaryotic organelles N-terminal methionine excision requires the sequential action of two activities, a peptide deformylase (PDF), which systematically removes the N-formyl group present on all nascent polypeptides and methionine aminopeptidase (MAP), which exscinds methionine specifically and depends on the previous removal of the N-formyl group. In Trypanosoma cruzi two genes encoding bacterial PDF homologues have been identified and referred to as TcPDF-1 and TcPDF-2. Here we report the biochemical characterization of a truncated soluble version of TcPDF-1 lacking the hydrophobic N-terminal domain that is active with the bacterial PDF substrate formyl-methionyl-alanyl-serine but, in contrast to other PDFs, is not inhibited by actinonin. The enzyme is strongly activated by Cu²⁺ and inhibited by Ni²⁺. Our results show that T. cruzi PDF exhibits unique features thus providing a new avenue for the design of potential inhibitors for use in the treatment of diseases caused by trypanosomatid parasites.
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