Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa |
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Authors: | Altincicek B Hintz M Sanderbrand S Wiesner J Beck E Jomaa H |
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Affiliation: | Institute of Biochemistry, Academic Hospital Centre, Justus-Liebig-University, Giessen, Germany. |
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Abstract: | Two Pseudomonas aeruginosa genes encoding the enzymes 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase, both involved in the mevalonate-independent biosynthesis of isoprenoids, have been expressed as recombinant enzymes in Escherichia coli. The purified P. aeruginosa DXP reductoisomerase was inhibited by submicromolar concentrations of the antibiotics fosmidomycin and FR-900098 in a well established method. A novel and convenient spectrophotometric assay was developed to determine activity and inhibition of P. aeruginosa DXP synthase. Fluoropyruvate is described as a first inhibitor of DXP synthase. |
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Keywords: | 1-Deoxy-D-xylulose 5-phosphate synthase 1-Deoxy-D-xylulose 5-phosphate reductoisomerase Inhibitor Pseudomonas aeruginosa |
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