Structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin
- Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502 (Japan)
- Biotechnology Research Center, University of Tokyo, Bunkyo-ku, Tokyo 113-8657 (Japan)
- Department of Applied Biology and Chemistry, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502 (Japan)
The crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) from Escherichia coli complexed with Mg{sup 2+}, NADPH and fosmidomycin was determined at 2.2 Å resolution. The structure showed a well defined loop conformation at the active site of DXR. The crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) from Escherichia coli complexed with Mg{sup 2+}, NADPH and fosmidomycin was solved at 2.2 Å resolution. DXR is the key enzyme in the 2-C-methyl-d-erythritol 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 Mg{sup 2+} was shifted by NADPH in the active site.
- OSTI ID:
- 22360353
- Journal Information:
- Acta Crystallographica. Section F, Vol. 63, Issue Pt 6; Other Information: PMCID: PMC2335089; PMID: 17554164; PUBLISHER-ID: sx5070; OAI: oai:pubmedcentral.nih.gov:2335089; Copyright (c) International Union of Crystallography 2007; Country of input: International Atomic Energy Agency (IAEA); ISSN 1744-3091
- Country of Publication:
- United Kingdom
- Language:
- English
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