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- W2767984573 abstract "Buthionine sulfoximine (BSO) induces decreased glutathione (GSH) and trypanothione [T(SH)2 ] pools in trypanosomatids, presumably because only gamma-glutamylcysteine synthetase (γECS) is blocked. However, some BSO effects cannot be explained by exclusive γECS inhibition; therefore, its effect on the T(SH)2 metabolism pathway in Trypanosoma cruzi was re-examined. Parasites exposed to BSO did not synthesize T(SH)2 even when supplemented with cysteine or GSH, suggesting trypanothione synthetase (TryS) inhibition by BSO. Indeed, recombinant γECS and TryS, but not GSH synthetase, were inhibited by BSO and kinetics and docking analyses on a TcTryS 3D model suggested BSO binding at the GSH site. Furthermore, parasites overexpressing γECS and TryS showed ~ 50% decreased activities after BSO treatment. These results indicated that BSO is also an inhibitor of TryS." @default.
- W2767984573 created "2017-11-17" @default.
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- W2767984573 date "2017-11-27" @default.
- W2767984573 modified "2023-10-14" @default.
- W2767984573 title "Buthionine sulfoximine is a multitarget inhibitor of trypanothione synthesis in<i>Trypanosoma cruzi</i>" @default.
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- W2767984573 doi "https://doi.org/10.1002/1873-3468.12904" @default.
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