Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups
Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups
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DOI：
10.1016/j.chembiol.2008.01.011
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发表时间：
2008-03-01
影响因子：
--
通讯作者：
Podobnik, Marjetka
中科院分区：
文献类型：
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作者：
Draskovic, Petra;Saiardi, Adolfo;Podobnik, Marjetka
真核细胞产生一系列含有焦磷酸键的多种肌醇多磷酸盐 (IP)。肌醇焦磷酸与多种细胞功能有关，并且越来越多的证据表明它们充当第二信使。肌醇六磷酸激酶 (IP6K) 能够将天然底物肌醇五磷酸 (IP5) 和肌醇六磷酸 (IP6) 转化为多种磷酸酐键数量不断增加的产物。在本研究中，我们对 IP5 和 IP6 的三种哺乳动物 IP6K 亚型合成的 IP 进行了结构分析。 NMR 和质量分析显示许多产物具有不同但特定的立体化学，由 IP6K 活性位点的结构定义。我们现在报道 IP6K 在肌醇环上合成焦磷酸（二磷酸）和三磷酸基团。所有三种 IP6K 亚型在体外和体内均具有相同的活性。
Eukaryotic cells produce a family of diverse inositol polyphosphates (IPs) containing pyrophosphate bonds. Inositol pyrophosphates have been linked to a wide range of cellular functions, and there is growing evidence that they act as second messengers. Inositol hexakisphosphate kinase (IP6K) is able to convert the natural substrates inositol pentakisphosphate (IP5) and inositol hexakisphosphate (IP6) to several products with an increasing number of phospho-anhydride bonds. In this study, we structurally analyzed IPs synthesized by three mammalian isoforms of IP6K from IP5 and IP6. The NMR and mass analyses showed a number of products with diverse, yet specific, stereochemistry, defined by the architecture of IP6K's active site. We now report that IP6K synthesizes both pyrophosphate (diphospho) as well as triphospho groups on the inositol ring. All three IP6K isoforms share the same activities both in vitro and in vivo.