On the functionality of a methionine sulfoxide reductase B from Trypanosoma cruzi.
Free Radic Biol Med
; 158: 96-114, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32682073
ABSTRACT
BACKGROUND:
Methionine is an amino acid susceptible to be oxidized to give a racemic mixture of R and S forms of methionine sulfoxide (MetSO). This posttranslational modification has been reported to occur in vivo under either normal or stress conditions. The reduction of MetSO to methionine is catalyzed by methionine sulfoxide reductases (MSRs), thiol-dependent enzymes present in almost all organisms. These enzymes can reduce specifically one or another of the isomers of MetSO (free and protein-bound). This redox modification could change the structure and function of many proteins, either concerned in redox or other metabolic pathways. The study of antioxidant systems in Trypanosoma cruzi has been mainly focused on the involvement of trypanothione, a specific redox component for these organisms. Though, little information is available concerning mechanisms for repairing oxidized methionine residues in proteins, which would be relevant for the survival of these pathogens in the different stages of their life cycle.METHODS:
We report an in vitro functional and in vivo cellular characterization of methionine sulfoxide reductase B (MSRB, specific for protein-bound MetSO R-enantiomer) from T. cruzi strain Dm28c.RESULTS:
MSRB exhibited both cytosolic and mitochondrial localization in epimastigote cells. From assays involving parasites overexpressing MSRB, we observed the contribution of this protein to increase the general resistance against oxidative damage, the infectivity of trypomastigote cells, and intracellular replication of the amastigote stage. Also, we report that epimastigotes overexpressing MSRB exhibit inhibition of the metacyclogenesis process; this suggesting the involvement of the proteins as negative modulators in this cellular differentiation. CONCLUSIONS AND GENERALSIGNIFICANCE:
This report contributes to novel insights concerning redox metabolism in T. cruzi. Results herein presented support the importance of enzymatic steps involved in the metabolism of L-Met and in repairing oxidized macromolecules in this parasite.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trypanosoma cruzi
/
Metionina Sulfóxido Redutases
Idioma:
En
Revista:
Free Radic Biol Med
Assunto da revista:
BIOQUIMICA
/
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article