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首页> 外文期刊>Acta crystallographica. Section D, Biological crystallography. >The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions
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The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals insights into its dual cytoplasmic and nuclear functions

机译：的结构bradyzoite-specific烯醇酶刚地弓形虫揭示其双重见解细胞质和核函数

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摘要

In addition to catalyzing a central step in glycolysis, enolase assumes a remarkably diverse set of secondary functions in different organisms, including transcription regulation as documented for the oncogene c-Myc promoterbinding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative tachyzoite stage. A 2.75 angstrom resolution crystal structure of bradyzoite enolase 1, the second structure to be reported of a bradyzoite-specific protein in Toxoplasma, captures an open conformational state and reveals that distinctive plant-like insertions are located on surface loops. The enolase 1 structure reveals that a unique residue, Glu164, in catalytic loop 2 may account for the lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter as demonstrated by gel retardation. Furthermore, direct physical interactions of both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in vivo using chromatin immunoprecipitation (ChIP) assays. Structural and biochemical studies reveal that T. gondii enolase functions are multifaceted, including the coordination of gene regulation in parasitic stage development. Enolase 1 provides a potential lead in the design of drugs against Toxoplasma brain cysts.
机译：除了催化中心介入糖酵解,烯醇酶假定一个非常多样化二次函数在不同生物,包括转录监管记录的致癌基因原癌基因promoterbinding蛋白质1。刚差异表达两个nuclear-localized,形似植物烯醇酶:烯醇酶1(TgENO1)阶段,潜在bradyzoite囊肿烯醇酶2 (TgENO2)迅速复制的tachyzoite阶段。晶体结构的bradyzoite烯醇酶1,第二次的报告结构在弓形虫bradyzoite-specific蛋白质,捕获一个开放的构象状态和显示独特的形似植物插入位于表面循环。显示一个独特的残渣,Glu164,催化循环2可能占较低活动的cyst-stage同工酶。TgENO1专门TTTTCT DNA结合的主题囊肿矩阵中抗原1 (TgMAG1)基因启动子的凝胶阻滞做了演示。此外,直接的物理相互作用核TgENO1和TgENO2 TgMAG1基因启动子中演示了使用染色质体内免疫沉淀反应(芯片)化验。生化研究表明,弓形虫烯醇酶功能是多方面的,包括协调的寄生基因调控阶段的发展。在抗弓形虫药物的设计脑囊肿。

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