Cysteine protease isoforms from Trypanosoma cruzi, cruzipain 2 and cruzain, present different substrate preference and susceptibility to inhibitors

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dc.contributor.authorLima, APCA
dc.contributor.authorReis, FCG dos
dc.contributor.authorServeau, C.
dc.contributor.authorLalmanach, G.
dc.contributor.authorJuliano, L.
dc.contributor.authorMenard, R.
dc.contributor.authorVernet, T.
dc.contributor.authorThomas, D. Y.
dc.contributor.authorStorer, A. C.
dc.contributor.authorScharfstein, J.
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionUniv Tours
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionNatl Res Council Canada
dc.date.accessioned2016-01-24T12:31:22Z
dc.date.available2016-01-24T12:31:22Z
dc.date.issued2001-04-25
dc.description.abstractCysteine-proteinases from parasitic protozoa have been recently characterized as factors of virulence and pathogenicity in several human and veterinary diseases. in Chagas' disease, the chronic infection caused by Trypanosoma cruzi, structure-functional studies on cysteine proteases were thus far limited to the parasite's major isoform, a cathepsin L-like lysosomal protease designated as cruzipain, cruzain or GP57/51. Encoded: by a large gene family, cruzipain is efficiently targeted by synthetic inhibitors, which prevent parasite intracellular growth and differentiation. We have previously demonstrated that the multicopy cruzipain gene family includes polymorphic sequences, which could encode functionally different isoforms. We report here a comparative kinetic study between cruzain, the archetype of the cruzipain family, and an isoform, termed cruzipain 2, which is expressed preferentially by the mammalian stages of T. cruzi. Heterologous expression of the catalytic domain of cruzipain 2 in Saccharomyces cerevisae yielded an enzyme that differs markedly from cruzain with respect to pH stability, substrate specificity and sensitivity to inhibition by natural and synthetic inhibitors of cysteine proteases. We suggest that the structural-functional diversification imparted by genetic polymorphism or cruzipain genes may have contributed to T. cruzi adaptation to vertebrate hosts. (C) 2001 Elsevier Science B.V. All rights reserved.en
dc.description.affiliationUFRJ, CCS, Inst Biofis Carlos Chagas Filho, Lab Mol Immunol, BR-21944900 Rio de Janeiro, RJ, Brazil
dc.description.affiliationUniv Tours, INSERM, EMIU 00 10, Enzymol & Prot Chem Lab, F-37032 Tours, France
dc.description.affiliationUNIFESP, INFAR, Dept Biophys, São Paulo, SP, Brazil
dc.description.affiliationNatl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada
dc.description.affiliationUnifespUNIFESP, INFAR, Dept Biophys, São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent41-52
dc.identifierhttp://dx.doi.org/10.1016/S0166-6851(01)00236-5
dc.identifier.citationMolecular and Biochemical Parasitology. Amsterdam: Elsevier B.V., v. 114, n. 1, p. 41-52, 2001.
dc.identifier.doi10.1016/S0166-6851(01)00236-5
dc.identifier.issn0166-6851
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/26531
dc.identifier.wosWOS:000168791500004
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofMolecular and Biochemical Parasitology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectTrypanosoma cruzien
dc.subjectcysteine proteaseen
dc.subjectcruzipainen
dc.subjectisoformsen
dc.subjectspecificityen
dc.subjectexpressionen
dc.titleCysteine protease isoforms from Trypanosoma cruzi, cruzipain 2 and cruzain, present different substrate preference and susceptibility to inhibitorsen
dc.typeinfo:eu-repo/semantics/article
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