Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects eight million individuals, primarily in Latin America. Currently there is no cure for chronic T. cruzi infections. Unlike humans, this parasite use a variety of sterols (e.g. ergosterol, 24-ethyl-cholesta-5,7,22-trien-3 beta ol, and its 22-dihydro analogs), rather than cholesterol in their cell membranes, so inhibiting endogenous sterol biosynthesis is an important therapeutic target. Here, we report the first structure of the parasite's squalene synthase, which catalyzes the first committed step in sterol biosynthesis, as well as the structures of a broad range of squalene synthase inhibitors active against the clinically relevant intracellular stages, opening the way to new approaches to treating this neglected tropical disease.
Vyšlo v časopise: Squalene Synthase As a Target for Chagas Disease Therapeutics. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004114 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004114
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