The major cysteinyl proteinase from Trypanosoma cruzi: structural and functional properties
Ciênc. cult. (Säo Paulo)
;
45(5): 322-9, Sept.-Oct. 1993. ilus
Article
Dans Anglais
| LILACS
| ID: lil-200100
RESUMO
New opportunities to develop structure-based strategies for design of antiparasite drugs have emerged from studies of a family of structurally homologous cysteinyl proteinases, recently identified in several pathogenic parasites. Research on the major cysteinyl proteinase from T. cruzi (designated as cruzain, cruzipain or GP57/51) has rapidly progressed, due to independent studies conducted in Buenos Aires, Rio de Janeiro and San Francisco. The biochemical heterogeneity of this developmentally regulated group of glycoproteins is at least in part determined by genetic polymorphism. Distinguished from mammalian lysosomal cathepsins (L/S/B) by the presence of a long COOH-terminus, these single chained proteins are encoded by multiple copies of polymorphic genes. Nonconservative amino acid substitutions appear to concentrate in the papain-like catalytic domain, and may impart different substrate specificity properties to cruzipain variants expressed at the various stages of parasite development. Notably, the replication and differentiation of T. cruzi in infected cells is critically dependent on the activity of cathepsin L-like cruzipains, expressed by intracellular amastigotes. The goal of improving target selectivity of cruzipain inhibitors may be now pursued, based on clues derived from the recently elucidated crystal structure of recombinant cruzain. Concurrent with progress made in the study of cruzipain's role in parasite physiology, these proteinases have beem recognized as major antigens in chronically infected patients. By stimulating antigen specific T cells to release gamma-interferon to host tissues, cruzipain may further promote inflammation thereby contributing to pathology. Ongoing studies should determine if the proteolytic activity of cruzipain can also contribute to parasite-induced tissue damage or to the immunoregulatory abnormalities associated with Chagas'disease.
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Indice:
LILAS (Amériques)
Sujet Principal:
Trypanosoma cruzi
/
Cysteine proteases
/
Antiparasitaires
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
Ciênc. cult. (Säo Paulo)
Thème du journal:
Science
Année:
1993
Type:
Article
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