CRUZIPAIN, THE MAJOR CYSTEINE PROTEINASE FROM THE PROTOZOAN PARASITE TRYPANOSOMA-CRUZI

Trypanosoma cruzi, the parasitic protozoan which causes the American T rypanosomiasis, Chagas disease, contains a major cysteine proteinase ( CP), cruzipain. The enzyme belongs to the papain family, but contains, as other CPs from Trypanosomatids, an unusual C-terminal extension. T his C-terminal domain contains a number of post-translational modifica tions and is responsible for the immunodominant antigenic character of cruzipain in natural human infections. In addition, this domain is pr obably the cause of most of the microheterogeneities found in natural cruzipain. Irreversible inhibitors of CPs are able to block the parasi te's life cycle at the differentiation steps, suggesting an essential role for CPs for parasite survival, and opening up possibilities of de veloping new chemotherapeutic agents against Chagas disease based on s pecific cruzipain inhibitors.