恶性疟原虫1-脱氧-D-木酮糖5-磷酸还原异构酶的结晶及初步X射线晶体学研究
Crystallization and preliminary X-ray crystallographic study of 1-deoxy-D-xylulose 5-phosphate reductoisomerase from Plasmodium falciparum.
作者信息
Umeda Tomonobu, Tanaka Nobutada, Kusakabe Yoshio, Nakanishi Masayuki, Kitade Yukio, Nakamura Kazuo T
机构信息
School of Pharmacy, Showa University, Tokyo 142-8555, Japan.
出版信息
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Mar 1;66(Pt 3):330-2. doi: 10.1107/S1744309110001739. Epub 2010 Feb 25.
Abstract
The nonmevalonate pathway of isoprenoid biosynthesis present in Plasmodium falciparum is known to be an effective target for antimalarial drugs. The second enzyme of the nonmevalonate pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), catalyzes the transformation of 1-deoxy-D-xylulose 5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP). For crystallographic studies, DXR from the human malaria parasite P. falciparum (PfDXR) was overproduced in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method in the presence of NADPH. X-ray diffraction data to 1.85 A resolution were collected from a monoclinic crystal form belonging to space group C2 with unit-cell parameters a = 168.89, b = 59.65, c = 86.58 A, beta = 117.8 degrees. Structural analysis by molecular replacement is in progress.
摘要
已知恶性疟原虫中存在的类异戊二烯生物合成的非甲羟戊酸途径是抗疟药物的有效靶点。非甲羟戊酸途径的第二种酶，1-脱氧-D-木酮糖-5-磷酸还原异构酶（DXR），催化1-脱氧-D-木酮糖-5-磷酸（DXP）转化为2-C-甲基-D-赤藓糖醇-4-磷酸（MEP）。为了进行晶体学研究，来自人类疟原虫恶性疟原虫（PfDXR）的DXR在大肠杆菌中过量表达，在NADPH存在下使用悬滴气相扩散法进行纯化和结晶。从属于空间群C2的单斜晶体形式收集了分辨率为1.85 Å的X射线衍射数据，其晶胞参数为a = 168.89，b = 59.65，c = 86.58 Å，β = 117.8°。正在通过分子置换进行结构分析。
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