Yajima Shunsuke, Hara Kodai, Iino Daisuke, Sasaki Yasuyuki, Kuzuyama Tomohisa, Ohsawa Kanju, Seto Haruo
Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jun 1;63(Pt 6):466-70. doi: 10.1107/S1744309107024475. Epub 2007 May 31.
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.
大肠杆菌中与镁离子（Mg(2+)）、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）及磷霉素结合的1-脱氧-D-木酮糖5-磷酸还原异构酶（DXR）的晶体结构在2.2埃分辨率下得到解析。DXR是2-C-甲基-D-赤藓糖醇4-磷酸途径中的关键酶，也是磷霉素等抗疟药物的有效作用靶点。在晶体结构中，清晰观察到覆盖活性位点的柔性环的电子密度，表明底物结合时DXR具有有序的构象。另一方面，未观察到NADPH烟酰胺核糖部分的电子密度，且活性位点中锚定Mg(2+)的天冬氨酸149（Asp149）的位置被NADPH改变。
