1H, 13C and 15N resonance assignment of the cytosolic dithiol glutaredoxin 1 from the pathogen Trypanosoma brucei.

Monica Stefani 1 Mattia Sturlese 1, 2 Bruno Manta 3, 4 Frank Löhr 5 Stefano Mammi 1 Marcelo Comini 3 Massimo Bellanda 1
1 Department of Chemical Sciences [Padova]
2 Department of Pharmaceutical and Pharmacological Sciences [Padova]
3 Institut Pasteur de Montevideo
4 UCUR - Universidad de la República [Montevideo]
5 Institute of Biophysical Chemistry [Frankfurt]
Abstract : Trypanosomatids are parasites responsible for several tropical and subtropical diseases, such as Chaga's disease, sleeping sickness and Leishmaniasis. In contrast to the mammalian host, the thiol-redox metabolism of these pathogens depends on trypanothione [bis-glutathionylspermidine, T(SH)2] instead of glutathione (GSH) providing a set of lineage-specific proteins as drug target candidates. Glutaredoxins (Grx) are ubiquitous small thiol-disulfide oxidoreductases that belong to the thioredoxin-fold family. They play a central role in redox homeostasis and iron sulfur-cluster biogenesis. Each species, including trypanosomes, possesses its own set of isoforms distributed in different subcellular compartments. The genome of trypanosomatids encodes for two class I (dithiolic) Grxs named 2-C-Grx1 and 2-C-Grx2. Both proteins were shown to efficiently reduce different disulfides at the expenses of T(SH)2 using a mechanism that involves the two cysteines in the active site. Moreover, the cytosolic Trypanosoma brucei 2-C-Grx1 but not the mitochondrial 2-C-Grx2 was able to coordinate an iron-sulfur cluster with T(SH)2 or GSH as ligand. As a first step to unravel the structural basis for the specificity observed in the trypanosomal glutaredoxins, we present here the NMR resonance assignment of 2-C-Grx1 from the parasite T. brucei brucei.
Keywords : Glutaredoxins Iron–sulfur cluster NMR Trypanosome Trypanothione
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Journal articles
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Submitted on : Monday, April 3, 2017 - 7:37:09 PM
Last modification on : Monday, October 8, 2018 - 5:44:06 PM

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Monica Stefani, Mattia Sturlese, Bruno Manta, Frank Löhr, Stefano Mammi, et al.. 1H, 13C and 15N resonance assignment of the cytosolic dithiol glutaredoxin 1 from the pathogen Trypanosoma brucei.. Biomolecular NMR Assignments, Springer, 2016, 10 (1), pp.85-8. ⟨10.1007/s12104-015-9643-x⟩. ⟨pasteur-01501052⟩

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