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Article Dans Une Revue Biochemical Journal Année : 2008

Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependant peroxidases

Magnus S Alphey
  • Fonction : Auteur
Janine Konig
  • Fonction : Auteur

Résumé

Trypanosoma brucei tryparedoxin-dependant peroxidase (TbTDPX) is a genetically validated drug target in the fight against African sleeping sickness. Despite its similarity to members of the glutathione peroxidase (GPX) family, TbTDPX2 is functional as a monomer, lacks a selenocysteine residue, relying instead on peroxidatic and resolving cysteines for catalysis and uses tryparedoxin rather than glutathione as electron donor. Kinetic studies indicate a saturable ping-pong mechanism, unlike selenium-dependent GPXs which display infinite Km and Vmax values. The structure of the reduced enzyme at 2.1 Å-resolution reveals that the catalytic thiol groups are widely separated (19 Å) and thus unable to form a disulphide bond without a large conformational change in the secondary structure architecture, as reported for certain plant GPXs. A model of the oxidized enzyme structure is presented and the implications for small molecule inhibition are discussed.

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hal-00479020 , version 1 (30-04-2010)

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Magnus S Alphey, Janine Konig, Alan H Fairlamb. Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependant peroxidases. Biochemical Journal, 2008, 414 (3), pp.375-381. ⟨10.1042/BJ20080889⟩. ⟨hal-00479020⟩

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