Trypanosoma cruzi trans-sialidase in complex with a neutralizing antibody: structure/function studies towards the rational design of inhibitors.

Trans-sialidase (TS), a virulence factor from Trypanosoma cruzi, is an enzyme playing key roles in the biology of this protozoan parasite. Absent from the mammalian host, it constitutes a potential target for the development of novel chemotherapeutic drugs, an urgent need to combat Chagas' disease. TS is involved in host cell invasion and parasite survival in the bloodstream.

A functional network of intramolecular cross-reacting epitopes delays the elicitation of neutralizing antibodies to Trypanosoma cruzi trans-sialidase.

Trypanosoma cruzi trans-sialidase (TS) constitutes a key molecule in both the establishment of the infection and in the development of pathologic abnormalities associated with Chagas disease. Several cross-reactive epitopes located in its catalytic region were previously identified. In the present study, a panel of enzymes altered in these epitopes were generated to analyze their in vivo significance.