On the mechanism and rate of gold incorporation into thiol-dependent flavoreductases. - RIIP - Réseau International des Instituts Pasteur Access content directly
Journal Articles Journal of Inorganic Biochemistry Year : 2012

On the mechanism and rate of gold incorporation into thiol-dependent flavoreductases.

Abstract

NADPH-dependent flavoreductases are important drug targets. During their enzymatic cycle thiolates and selenolates that have high affinity for transition metals are generated. Auranofin (AF), a gold-containing compound, is classified by the World Health Organization as an antirheumatic agent and it is indicated as the scaffold for the development of new anticancer and antiparasitic drugs. AF inhibits selenocysteine-containing flavoreductases (thioredoxin reductase and thioredoxin glutathione reductase) more effectively than non Se-containing ones (glutathione reductase); this preference has been ascribed to the high affinity of selenium for gold. We solved the 3D structure of the Se-containing Thioredoxin Glutathione Reductase from the human parasite Schistosoma mansoni complexed with Au and our results challenge this view: we believe that the relative velocity of the reaction rather than the relative affinity, depends on the presence of Sec residues, which appear to dictate AF selectivity.
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Dates and versions

pasteur-00952028 , version 1 (26-02-2014)

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Fulvio Saccoccia, Francesco Angelucci, Giovanna Boumis, Maurizio Brunori, Adriana E Miele, et al.. On the mechanism and rate of gold incorporation into thiol-dependent flavoreductases.. Journal of Inorganic Biochemistry, 2012, 108, pp.105-11. ⟨10.1016/j.jinorgbio.2011.11.005⟩. ⟨pasteur-00952028⟩

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