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-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.
Yajima
Shunsuke
S
Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan. yshun@nodai.ac.jp
Hara
Kodai
K
Iino
Daisuke
D
Sasaki
Yasuyuki
Y
Kuzuyama
Tomohisa
T
Ohsawa
Kanju
K
Seto
Haruo
H
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
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