1-Deoxy-D-xylulose 5-phosphate reductoisomerase: an overview.
The methylerythritol phosphate pathway to isoprenoids, an alternate biosynthetic route present in many bacteria, algae, plants, and the malarial parasite Plasmodium falciparum, has become an attractive target for the development of new antimalarial and antibacterial compounds. The second enzyme in this pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR; EC 1.1.1.267), has been shown to be the molecular target for fosmidomycin, a promising antimalarial drug. This enzyme converts 1-deoxy-D-xylulose 5-phosphate (DXP) into the branched compound 2-C-methyl-D-erythritol 4-phosphate (MEP). The transformation of DXP into MEP requires an isomerization, followed by a NADPH-dependent reduction. The discovery of DXR, its subsequent characterization, and the identification of inhibitors will be presented.
Proteau
Philip J
PJ
Department of Pharmaceutical Sciences, College of Pharmacy, Pharmacy Building, Room 203, Oregon State University, Corvallis 97331-3507, USA. phil.proteau@oregonstate.edu
D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005578:Fosfomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D000962:Antimalarials; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D005578:Fosfomycin; C024640:fosmidomycin; C024639:3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases