DXS as a target for structure-based drug design

被引：11

作者：

Gierse, Robin Matthias ^{[1
]}

Redeem, Eswar ^{[1
]}

Diamanti, Eleonora ^{[1
]}

Wrenger, Carsten ^{[2
]}

Groves, Matthew R. ^{[3
]}

Hirsch, Anna K. H. ^{[1
]}

机构：

[1] Univ Groningen, Stratingh Inst Chem, Nijenborgh 7, NL-9747 AG Groningen, Netherlands

[2] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Unit Drug Discovery, Sao Paulo, Brazil

[3] Univ Groningen, Dept Pharm, Struct Biol Unit, Drug Design, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands

来源：

FUTURE MEDICINAL CHEMISTRY | 2017年 / 9卷 / 11期

关键词：

antibiotics; anti-infectives; DXS; malaria; methylerythritol phosphate pathway; protein crystallography; structure-based drug design; tuberculosis; 1-DEOXY-D-XYLULOSE 5-PHOSPHATE SYNTHASE; NON-MEVALONATE PATHWAY; METHYLERYTHRITOL 4-PHOSPHATE PATHWAY; ISOPRENOID BIOSYNTHESIS; PLASMODIUM-FALCIPARUM; CRYSTAL-STRUCTURE; SWISS-MODEL; INHIBITION; ENZYME; DRUGGABILITY;

D O I：

10.4155/fmc-2016-0239

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this review, we analyze the enzyme DXS, the first and rate-limiting protein in the methylerythritol 4-phosphate pathway. This pathway was discovered in 1996 and is one of two known metabolic pathways for the biosynthesis of the universal building blocks for isoprenoids. It promises to offer new targets for the development of anti-infectives against the human pathogens, malaria or tuberculosis. We mapped the sequence conservation of 1-deoxy-xylulose-5-phosphate synthase on the protein structure and analyzed it in comparison with previously identified druggable pockets. We provide a recent overview of known inhibitors of the enzyme. Taken together, this sets the stage for future structure-based drug design.

引用

页码：1277 / 1294

页数：18

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