Flavonoids: true or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase.
Fiche publication
Date publication
avril 2015
Journal
Bioorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GROSDEMANGE-BILLIARD Catherine
Tous les auteurs :
Tritsch D, Zinglé C, Rohmer M, Grosdemange-Billiard C
Lien Pubmed
Résumé
Flavonoids, due to their physical and chemical properties (among them hydrophobicity and metal chelation abilities), are potential inhibitors of the 1-deoxyxylulose 5-phosphate reductoisomerase and most of the tested flavonoids effectively inhibited its activity with encouraging IC50 values in the micromolar range. The addition of 0.01% Triton X100 in the assays led however, to a dramatic decrease of the inhibition revealing that a non-specific inhibition probably takes place. Our study highlights the possibility of erroneous conclusions regarding the inhibition of enzymes by flavonoids that are able to produce aggregates in micromolar range. Therefore, the addition of a detergent in the assays prevents possible false positive hits in high throughput screenings.
Mots clés
1-Deoxyxylulose 5-phosphate reductoisomerase, 2-C-methyl-D-erythritol 4-phosphate pathway, Flavonoids, Promiscuous inhibition
Référence
Bioorg Chem. 2015 Apr;59:140-4