Synthesis and Kinetic evaluation of an azido analogue of methylerythritol phosphate: a Novel Inhibitor of E. coli YgbP/IspD.
Fiche publication
Date publication
décembre 2018
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr WAGNER Alain
Tous les auteurs :
Baatarkhuu Z, Chaignon P, Borel F, Ferrer JL, Wagner A, Seemann M
Lien Pubmed
Résumé
As multidrug resistant pathogenic microorganisms are a serious health menace, it is crucial to continuously develop novel medicines in order to overcome the emerging resistance. The methylerythritol phosphate pathway (MEP) is an ideal target for antimicrobial development as it is absent in humans but present in most bacteria and in the parasite Plasmodium falciparum. Here, we report the synthesis and the steady-state kinetics of a novel potent inhibitor (MEPN) of Escherichia coli YgbP/IspD, the third enzyme of the MEP pathway. MEPN inhibits E. coli YgbP/IspD in mixed type mode regarding both substrates. Interestingly, MEPN shows the highest inhibitory activity when compared to known inhibitors of E. coli YgbP/IspD. The mechanism of this enzyme was also studied by steady-state kinetic analysis and it was found that the substrates add to the enzyme in sequential manner.
Référence
Sci Rep. 2018 Dec 17;8(1):17892