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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Vázquez C,Mejia-Tlachi M,González-Chávez Z,Silva A,Rodríguez-Zavala JS,Moreno-Sánchez R,Saavedra Edoi
10.1002/1873-3468.12904subject
Has Abstractpub_date
2017-12-01 00:00:00pages
3881-3894issue
23eissn
0014-5793issn
1873-3468journal_volume
591pub_type
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