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

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

Autor Lima, APCA Google Scholar
Reis, FCG dos Google Scholar
Serveau, C. Google Scholar
Lalmanach, G. Google Scholar
Juliano, L. Google Scholar
Menard, R. Google Scholar
Vernet, T. Google Scholar
Thomas, D. Y. Google Scholar
Storer, A. C. Google Scholar
Scharfstein, J. Google Scholar
Instituição Universidade Federal do Rio de Janeiro (UFRJ)
Univ Tours
Universidade Federal de São Paulo (UNIFESP)
Natl Res Council Canada
Resumo Cysteine-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.
Palavra-chave Trypanosoma cruzi
cysteine protease
cruzipain
isoforms
specificity
expression
Idioma Inglês
Data de publicação 2001-04-25
Publicado em Molecular and Biochemical Parasitology. Amsterdam: Elsevier B.V., v. 114, n. 1, p. 41-52, 2001.
ISSN 0166-6851 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 41-52
Fonte http://dx.doi.org/10.1016/S0166-6851(01)00236-5
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000168791500004
Endereço permanente http://repositorio.unifesp.br/handle/11600/26531

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