Kinetic analyses and inhibition studies reveal novel features in peptide deformylase 1 from Trypanosoma cruzi

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• 作者：Carlos A. Rodrí ; gues-Poveda^a ; Guiomar Pé ; rez-Moreno^a ; Antonio E. Vidal^a ; Julio A. Urbina^b ; Dolores Gonzá ; lez-Pacanowska^a ; ^{dgonzalez@ipb.csic.es} ; Luis M. Ruiz-Pé ; rez^a
• 关键词：PDF ; peptide deformylase ; EDTA ; ethylenediaminetetraacetic acid ; f-MAS ; formyl-methionyl-alanyl-serine
• 刊名：Molecular and Biochemical Parasitology
• 出版年：2012
• 出版时间：March-April 2012
• 年：2012
• 卷：182
• 期：1-2
• 页码：83-87
• 全文大小：448 K

文摘

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.