Structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin

The crystal structure of 1-deoxy-D-xylulose5-phosphate reductoisomerase (DXR) from Escherichia coli complexed with Mg2+, NADPH and fosmidomycin was solved at 2.2 angstrom resolution. DXR is the key enzyme in the 2-C-methylderythritol 4-phosphate pathway and is an effective target of antimalarial drugs such as fosmidomycin. In the crystal structure, electron density for the flexible loop covering the active site was clearly observed, indicating the well ordered conformation of DXR upon substrate binding. On the other hand, no electron density was observed for the nicotinamide-ribose portion of NADPH and the position of Asp149 anchoring Mg2+ was shifted by NADPH in the active site.