Cysteine protease isoforms from Trypanosoma cruzi, cruzipain 2 and cruzain, present different substrate preference and susceptibility to inhibitors.
Mol Biochem Parasitol
; 114(1): 41-52, 2001 Apr 25.
Article
en En
| MEDLINE
| ID: mdl-11356512
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 of cruzipain genes may have contributed to T. cruzi adaptation to vertebrate hosts.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trypanosoma cruzi
/
Cisteína Endopeptidasas
/
Inhibidores de Cisteína Proteinasa
/
Proteínas Protozoarias
Aspecto:
Patient_preference
Límite:
Animals
Idioma:
En
Revista:
Mol Biochem Parasitol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Países Bajos