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首页> 外文期刊>Journal of Molecular Biology >Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids.
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Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids.

机译：2C-甲基-d-赤藓糖醇-2,4-环二磷酸合酶的结构涉及类戊二酸的甲羟戊酸非依赖性生物合成。

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摘要

Isoprenoids are biosynthesized from isopentenyl diphosphate and the isomeric dimethylallyl diphosphate via the mevalonate pathway or a mevalonate-independent pathway that was identified during the last decade. The non-mevalonate pathway is present in many bacteria, some algae and in certain protozoa such as the malaria parasite Plasmodium falciparum and in the plastids of higher plants, but not in mammals and archaea. Therefore, these enzymes have been recognised as promising drug targets. We report the crystal structure of Escherichia coli 2C- methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), which converts 4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate into 2C-methyl-d-erythritol 2,4-cyclodiphosphate and CMP in a Mg-dependent reaction. The protein forms homotrimers that tightly bind one zinc ion per subunit at the active site, which helps to position the substrate for direct attack of the 2-phosphate group on the beta-phosphate.
机译：异戊二烯是通过近十年来确定的甲羟戊酸途径或非甲羟戊酸依赖性途径，由异戊烯基二磷酸酯和异构体二甲基烯丙基二磷酸酯生物合成的。非甲羟戊酸途径存在于许多细菌，某些藻类和某些原生动物中，例如疟原虫恶性疟原虫和高等植物的质体中，而在哺乳动物和古细菌中则不存在。因此，这些酶被认为是有前途的药物靶标。我们报告了大肠杆菌2C-甲基-d-赤藓糖醇-2,4-环二磷酸合酶（IspF）的晶体结构，它会将4-diphosphocytidyl-2C-甲基-d-赤藓糖醇2-磷酸转化为2C-甲基-d-赤藓糖醇2,4-环二磷酸酯和CMP依赖于Mg。该蛋白质形成同三聚体，该同三聚体在活性位点每个亚基紧密结合一个锌离子，这有助于定位底物以直接攻击β-磷酸上的2-磷酸基团。

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