Open AccessStructure of 1‐deoxy‐ d ‐xylulose 5‐phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin
Author(s) -
Yajima Shunsuke,
Hara Kodai,
Iino Daisuke,
Sasaki Yasuyuki,
Kuzuyama Tomohisa,
Ohsawa Kanju,
Seto Haruo
Publication year - 2007
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309107024475
Subject(s) - active site , chemistry , stereochemistry , substrate (aquarium) , magnesium , nicotinamide , enzyme , crystallography , biochemistry , biology , organic chemistry , ecology
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 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 2+ was shifted by NADPH in the active site.