Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum

被引：20
|
作者：
Rekittke, Ingo [1 ]
Olkhova, Elena [2 ]
Wiesner, Jochen [1 ]
Demmer, Ulrike [2 ]
Warkentin, Eberhard [2 ]
Jomaa, Hassan [1 ]
Ermler, Ulrich [2 ]
机构：
[1] Univ Giessen, Med Klin Hamatol 4, D-35392 Giessen, Germany
[2] Max Planck Inst Biophys, D-60438 Frankfurt, Germany
来源：
FEBS LETTERS | 2013年 / 587卷 / 24期
关键词：
Isoprenoid biosynthesis; LytB; X-ray structure; Drug design; Plasmodium falciparum; ISOPRENOID BIOSYNTHESIS; ESCHERICHIA-COLI; ISPH PROTEIN; PATHWAY; ANTIMALARIAL; DISCOVERY; ENZYME; LYTB;
D O I：
10.1016/j.febslet.2013.10.029
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Terpenoid precursor biosynthesis occurs in human and many pathogenic organisms via the mevalonate and 2-C-methyl-D-erythritol-4-phosphate (MEP) pathways, respectively. We determined the X-ray structure of the Fe/S containing (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase (LytB) of the pathogenic protozoa Plasmodium falciparum which catalyzes the terminal step of the MEP pathway. The cloverleaf fold and the active site of P. falciparum LytB corresponds to those of the Aquifex aeolicus and Escherichia coli enzymes. Its distinct electron donor [2Fe-2S] ferredoxin was modeled to its binding site by docking calculations. The presented structural data provide a platform for a rational search of anti-malarian drugs. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：3968 / 3972
页数：5
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