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

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dc.contributor.authorGallo, Gloria [UNIFESP]
dc.contributor.authorRamos, Thiago Cesar Prata [UNIFESP]
dc.contributor.authorTavares, Fernanda
dc.contributor.authorRocha, Antonio Augusto [UNIFESP]
dc.contributor.authorMachi, Emerson
dc.contributor.authorSchenkman, Sergio [UNIFESP]
dc.contributor.authorBahia, Diana [UNIFESP]
dc.contributor.authorPesquero, João Bosco [UNIFESP]
dc.contributor.authorWuertele, Martin [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionCtr Biol Mol Estrutural
dc.date.accessioned2016-01-24T14:16:45Z
dc.date.available2016-01-24T14:16:45Z
dc.date.issued2011-05-13
dc.description.abstractProtein 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.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Ciencia & Tecnol, BR-12231280 Sao Jose Dos Campos, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Morfol & Genet, BR-04023062 São Paulo, Brazil
dc.description.affiliationCtr Biol Mol Estrutural, Lab Nacl Luz Sincrotron, BR-13083100 Campinas, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Ciencia & Tecnol, BR-12231280 Sao Jose Dos Campos, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Morfol & Genet, BR-04023062 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent427-431
dc.identifierhttp://dx.doi.org/10.1016/j.bbrc.2011.04.038
dc.identifier.citationBiochemical and Biophysical Research Communications. San Diego: Academic Press Inc Elsevier Science, v. 408, n. 3, p. 427-431, 2011.
dc.identifier.doi10.1016/j.bbrc.2011.04.038
dc.identifier.fileWOS000290926400012.pdf
dc.identifier.issn0006-291X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33701
dc.identifier.wosWOS:000290926400012
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBiochemical and Biophysical Research Communications
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectProtein tyrosine phosphataseen
dc.subjectTrypanosoma cruzien
dc.subjectChagas' diseaseen
dc.subjectRecombinant expressionen
dc.titleBiochemical characterization of a protein tyrosine phosphatase from Trypanosoma cruzi involved in metacyclogenesis and cell invasionen
dc.typeinfo:eu-repo/semantics/article
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