Biochemical characterization of a protein tyrosine phosphatase from Trypanosoma cruzi involved in metacyclogenesis and cell invasion

Biochemical characterization of a protein tyrosine phosphatase from Trypanosoma cruzi involved in metacyclogenesis and cell invasion

Author Gallo, Gloria Autor UNIFESP Google Scholar
Ramos, Thiago Cesar Prata Autor UNIFESP Google Scholar
Tavares, Fernanda Google Scholar
Rocha, Antonio Augusto Autor UNIFESP Google Scholar
Machi, Emerson Google Scholar
Schenkman, Sergio Autor UNIFESP Google Scholar
Bahia, Diana Autor UNIFESP Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Wuertele, Martin Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Ctr Biol Mol Estrutural
Abstract Protein tyrosine phosphatases (PTPs) form a large family of enzymes involved in the regulation of numerous cellular functions in eukaryotes. Several protein tyrosine phosphatases have been recently identified in trypanosomatides. Here we report the purification and biochemical characterization of TcPTP1, a protein tyrosine phosphatase from Trypanosoma cruzi, the causing agent of Chagas' disease. the enzyme was cloned and expressed recombinantly in Escherichia coli and purified by Ni-affinity chromatography. Biochemical characterization of recombinant TcPTP1 with the PTP pseudo-substrate pNPP allowed the estimation of a Michaelis-Menten constant K-m of 4.5 mM and a k(cat) of 2.8 s(-1). We were able to demonstrate inhibition of the enzyme by the PTP1b inhibitor BZ3, which on its turn was able to accelerate the differentiation of epimastigotes into metacyclic forms of T. cruzi induced by nutritional stress. Additionally, this compound was able to inhibit by 50% the infectivity of T. cruzi trypomastigotes in a separate cellular assay. in conclusion our results indicate that TcPTP1 is of importance for cellular differentiation and invasivity of this parasite and thus is a valid target for the rational drug design of potential antibiotics directed against T. cruzi. (C) 2011 Elsevier Inc. All rights reserved.
Keywords Protein tyrosine phosphatase
Trypanosoma cruzi
Chagas' disease
Recombinant expression
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Date 2011-05-13
Published in Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc Elsevier Science, v. 408, n. 3, p. 427-431, 2011.
ISSN 0006-291X (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 427-431
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000290926400012

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