Thioredoxin glutathione reductase (TGR) is a key flavoenzyme expressed by schistosomes that bridges two detoxification pathways crucial for the parasite survival in the host's organism. In this article we report the crystal structure (at 2.2 Å resolution) of TGR from Schistosoma mansoni (SmTGR), deleted in the last two residues. The structure reveals the peculiar architecture of this chimeric enzyme: the small Glutaredoxin (Grx) domain at the N-terminus is joined to the large thioredoxin reductase (TR) one via an extended complementary surface, involving residues not conserved in the Grx superfamily; the TR domain interacts with an identical partner via its C-terminal domain, forming a dimer with a twisted “W” shape. Although lacking the penultimate Selenocysteine residue (Sec), the enzyme is still able to reduce oxidized glutathione. These data update the interpretation of the interdomain communication in TGR enzymes. The possible function of this enzyme in pathogenic parasites is discussed.

Glutathione reductase and thioredoxin reductase at the crossroad: The structure of Schistosoma mansoni thioredoxin glutathione reductase / Angelucci, Francesco; Miele, Adriana Erica; Boumis, Giovanna; Dimastrogiovanni, Daniela; Brunori, Maurizio; Bellelli, Andrea. - In: PROTEINS. - ISSN 0887-3585. - STAMPA. - 72:(2008), pp. 936-945. [10.1002/prot.21986]

Glutathione reductase and thioredoxin reductase at the crossroad: The structure of Schistosoma mansoni thioredoxin glutathione reductase.

ANGELUCCI, Francesco;MIELE, Adriana Erica;BOUMIS, Giovanna;DIMASTROGIOVANNI, Daniela;BRUNORI, Maurizio;BELLELLI, Andrea
2008

Abstract

Thioredoxin glutathione reductase (TGR) is a key flavoenzyme expressed by schistosomes that bridges two detoxification pathways crucial for the parasite survival in the host's organism. In this article we report the crystal structure (at 2.2 Å resolution) of TGR from Schistosoma mansoni (SmTGR), deleted in the last two residues. The structure reveals the peculiar architecture of this chimeric enzyme: the small Glutaredoxin (Grx) domain at the N-terminus is joined to the large thioredoxin reductase (TR) one via an extended complementary surface, involving residues not conserved in the Grx superfamily; the TR domain interacts with an identical partner via its C-terminal domain, forming a dimer with a twisted “W” shape. Although lacking the penultimate Selenocysteine residue (Sec), the enzyme is still able to reduce oxidized glutathione. These data update the interpretation of the interdomain communication in TGR enzymes. The possible function of this enzyme in pathogenic parasites is discussed.
thioredoxin reductase; glutaredoxin; supramolecular assembly; structure-based drug design; redox-detoxification pathway; SCHISTOSOMIASIS
01 Pubblicazione su rivista::01a Articolo in rivista
Glutathione reductase and thioredoxin reductase at the crossroad: The structure of Schistosoma mansoni thioredoxin glutathione reductase / Angelucci, Francesco; Miele, Adriana Erica; Boumis, Giovanna; Dimastrogiovanni, Daniela; Brunori, Maurizio; Bellelli, Andrea. - In: PROTEINS. - ISSN 0887-3585. - STAMPA. - 72:(2008), pp. 936-945. [10.1002/prot.21986]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/224327
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