Chagas disease or American trypanosomiasis is caused by Trypanosoma cruzi, a flagellated parasite that is transmitted to mammals through infected feces of hematophagous triatomine bugs. Around 6 to 7 million people in the world are infected with this parasite, with 12,000 deaths per year standing out for the most part in the main rural areas of America. The chagas disease occurs in two phases. The acute phase develops during the first two months of the onset of the infection and the symptoms in around 70 to 80% of cases are null. When passing to the chronic phase, around 30% of patients may present cardiac disorders and 10% digestive disorders that can lead to death. The drugs used for the treatment of Chagas disease are nifurtimox and benzimidazole, which have shown effectiveness during the acute phase of the disease, and not in the chronic phase. In addition, adverse effects during treatment lead to its abandonment, making it necessary to seek new therapeutic strategies. The enzymes that participate in the synthesis of Cys , are candidates to develop antichagasic drugs, this is because some of these enzymes are exclusive to T. cruzi or have substantial differences from the enzymes of the host. Cystathionine β synthase is an enzyme that participates in the synthesis of Cys and that could be a good therapeutic target due to its structural difference compared to that present in humans and its great catalytic versatility. The canonical reaction of CBS consists of the condensation of homocysteine and Serine for the formation of Cystationine, constituting the first step for the synthesis of Cys via the transsulfuration pathway. However, CBS can catalyze reactions using multiple substrates such as O acetylserine , sulfur, and Cys, leading to the formation of multiple products. Although some of these reactions have been evaluated, a complete kinetic characterization has not been carried out to understand their importance within the Cys synthesis pathways. Therefore, the main objective of this project is the characterization of the non-canonical reactions of CBS. The results obtained from this work will allow us to evaluate the importance of non canonical reactions within the Cys synthesis pathways in T. cruzi and will contribute to the design of new therapeutic strategies.

Kinetic study of non canonical reactions of cystathionine β synthase from T cruzi

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