4 years ago

Buthionine sulfoximine is a multi-target inhibitor of trypanothione synthesis in Trypanosoma cruzi

José Salud Rodríguez-Zavala, Rafael Moreno-Sánchez, Zabdi González-Chávez, Marlen Mejía-Tlachi, Citlali Vázquez, Aketzalli Silva, Emma Saavedra
Buthionine sulfoximine (BSO) induces decreased 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 glutathione, suggesting trypanothione synthetase (TryS) inhibition by BSO. Indeed, recombinant γECS and TryS, but not glutathione synthetase, were inhibited by BSO and kinetics and docking analyses on a TcTryS 3D model suggested BSO binding at the glutathione 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. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/1873-3468.12904

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.