title: 1H, 13C and 15N resonance assignment of the cytosolic dithiol glutaredoxin 1 from the pathogen Trypanosoma brucei.
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.
authors.affiliation: Department of Chemical Sciences, Università degli Studi di Padova, Via Marzolo 1, 35131, Padova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Stefani
authors.affiliation: Department of Chemical Sciences, Università degli Studi di Padova, Via Marzolo 1, 35131, Padova, Italy.|Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, Università degli Studi di Padova, Via Marzolo 5, 35131, Padova, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Sturlese
authors.affiliation: Laboratory Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay.|Laboratorio de Fisicoquímica Biológica, Facultad de Ciencias, Instituto de Química Biológica, Universidad de la República, Igua 4225, 11400, Montevideo, Uruguay.
authors.forename: Bruno
authors.initials: B
authors.lastname: Manta
authors.affiliation: Centre for Biomolecular Magnetic Resonance, Institute of Biophysical Chemistry, Goethe-University, Frankfurt, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Löhr
authors.affiliation: Department of Chemical Sciences, Università degli Studi di Padova, Via Marzolo 1, 35131, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mammi
authors.affiliation: Laboratory Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Comini
authors.affiliation: Department of Chemical Sciences, Università degli Studi di Padova, Via Marzolo 1, 35131, Padova, Italy. massimo.bellanda@unipd.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bellanda
mesh_terms: D000595:Amino Acid Sequence; D002247:Carbon Isotopes; D020134:Catalytic Domain; D003600:Cytosol / Q000378:metabolism*; D054477:Glutaredoxins / Q000737:chemistry*; D006801:Humans; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D014050:Toluene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D014316:Tritium; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D054477:Glutaredoxins; D009587:Nitrogen Isotopes; D014316:Tritium; D014050:Toluene; C004848:dithiol
keywords: Glutaredoxins; Iron–sulfur cluster; NMR; Trypanosome; Trypanothione