title: Structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin.
abstract: The crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) from Escherichia coli complexed with Mg(2+), NADPH and fosmidomycin was solved at 2.2 A 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(2+) was shifted by NADPH in the active site.
authors.affiliation: Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan. yshun@nodai.ac.jp
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yajima
authors.forename: Kodai
authors.initials: K
authors.lastname: Hara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iino
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kuzuyama
authors.forename: Kanju
authors.initials: K
authors.lastname: Ohsawa
authors.forename: Haruo
authors.initials: H
authors.lastname: Seto
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000737:chemistry* / Q000378:metabolism; D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D009249:NADP / Q000737:chemistry* / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary
chemical_list: D000962:Antimalarials; D009097:Multienzyme Complexes; D005578:Fosfomycin; D009249:NADP; C024640:fosmidomycin; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases; D008274:Magnesium