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首页> 外文期刊>Proteins: Structure, Function, and Genetics >Crystal structure of phosphoglucose isomerase from Trypanosoma brucei complexed with glucose-6-phosphate at 1.6 A resolution.
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Crystal structure of phosphoglucose isomerase from Trypanosoma brucei complexed with glucose-6-phosphate at 1.6 A resolution.

机译：来自布鲁氏锥虫的磷酸葡萄糖异构酶的晶体结构与葡萄糖-6-磷酸复合，分辨率为1.6A。

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摘要

Enzymes of glycolysis in Trypanosoma brucei have been identified as potential drug targets for African sleeping sickness because glycolysis is the only source of ATP for the bloodstream form of this parasite. Several inhibitors were previously reported to bind preferentially to trypanosomal phosphoglucose isomerase (PGI, the second enzyme in glycolysis) than to mammalian PGIs, which suggests that PGI might make a good target for species-specific drug design. Herein, we report recombinant expression, purification, crystallization and X-ray crystal structure determination of T. brucei PGI. One structure solved at 1.6 A resolution contains a substrate, D-glucose-6-phosphate, in an extended conformation in the active site. A second structure solved at 1.9 A resolution contains a citrate molecule in the active site. The structures are compared with the crystal structures of PGI from humans and from Leishmania mexicana. The availability of recombinant tPGI and its first high-resolution crystal structures areinitial steps in considering this enzyme as a potential drug target.
机译：布氏锥虫中的糖酵解酶已​​被确定为非洲昏睡病的潜在药物靶标，因为糖酵解是该寄生虫血流形式的ATP的唯一来源。以前有报道称几种抑制剂优先结合锥虫磷酸葡萄糖异构酶（糖酵解中的第二种酶）而不是哺乳动物PGI，这表明PGI可能成为特定物种药物设计的良好靶标。在本文中，我们报告了布鲁氏锥虫PGI的重组表达，纯化，结晶和X射线晶体结构测定。一种以1.6 A分辨率解析的结构包含一个在活性位点呈延长构象的底物D-葡萄糖-6-磷酸酯。在1.9 A分辨率下解析的第二个结构在活性位点包含一个柠檬酸盐分子。将这些结构与人类和墨西哥利什曼原虫的PGI晶体结构进行了比较。重组tPGI的可用性及其第一个高分辨率晶体结构是将这种酶视为潜在药物靶标的初始步骤。

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