• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase
【24h】

Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase

机译：双功能异柠檬酸脱氢酶激酶/磷酸酶的结构

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The Escherichia colt isocitrate dehydrogenase kinase/phosphatase (AceK) is a unique bifunctional enzyme that phosphorylates or dephosphorylates isocitrate dehydrogenase (ICDH) in response to environmental changes, resulting in the inactivation or, respectively, activation of ICDH. ICDH inactivation short-circuits the Krebs cycle by enabling the glyoxlate bypass. It was the discovery of AceK and ICDH that established the existence of protein phos-phorylation regulation in prokaryotes. As a 65-kDa protein, AceK is significantly larger than typical eukaryotic protein kinases. Apart from the ATP-binding motif, AceK does not share sequence homo-logy with any eukaryotic protein kinase or phosphatase. Most intriguingly, AceK possesses the two opposing activities of protein kinase and phosphatase within one protein, and specifically recognizes only intact ICDH. Additionally, AceK has strong ATPase activity9. It has been shown that AceK kinase, phosphatase and ATPase activities reside at the same site, although the molecular basis of such multifunctionality and its regulation remains completely unknown. Here we report the structures of AceK and its complex with ICDH. The AceK structure reveals a eukaryotic protein-kinase-like domain containing ATP and a regulatory domain with a novel fold. As an AceK phosphatase activator and kinase inhibitor, AMP is found to bind in an allosteric site between the two AceK domains. An AMP-mediated conformational change exposes and shields ATP, acting as a switch between AceK kinase and phosphatase activities, and ICDH-binding induces further conformational change for AceK activation. The substrate recognition loop of AceK binds to the ICDH dimer, allowing higher-order substrate recognition and interaction, and inducing critical conformational change at the phosphorylation site of ICDH.
机译：大肠杆菌柯尔特异柠檬酸脱氢酶激酶/磷酸酶（AceK）是一种独特的双功能酶，可响应环境变化而使异柠檬酸脱氢酶（ICDH）磷酸化或去磷酸化，从而导致ICDH失活或活化。 ICDH失活通过启用乙二醛旁路而使克雷布斯循环短路。正是AceK和ICDH的发现确立了原核生物中蛋白质磷酸化调控的存在。作为65 kDa的蛋白质，AceK明显大于典型的真核蛋白激酶。除了ATP结合基序，AceK不与任何真核蛋白激酶或磷酸酶共享序列同源性。最有趣的是，AceK在一种蛋白质中具有蛋白激酶和磷酸酶的两个相反的活性，并且仅特异性识别完整的ICDH。此外，AceK具有很强的ATPase活性9。已经显示出AceK激酶，磷酸酶和ATP酶活性位于同一位点，尽管这种多功能性及其调节的分子基础仍然是完全未知的。在这里，我们报告AceK的结构及其与ICDH的复合体。 AceK结构揭示了含有ATP的真核蛋白激酶样结构域和具有新颖折叠的调节结构域。作为AceK磷酸酶激活剂和激酶抑制剂，发现AMP结合在两个AceK域之间的变构位点中。 AMP介导的构象变化暴露并屏蔽ATP，充当AceK激酶和磷酸酶活性之间的转换，而ICDH结合诱导进一步的构象变化以激活AceK。 AceK的底物识别环与ICDH二聚体结合，可进行更高级的底物识别和相互作用，并在ICDH的磷酸化位点诱导关键的构象变化。

著录项

  • 来源
    《Nature》 |2010年第7300期|P.961-965|共5页
  • 作者

    Jimin Zheng; Zongchao Jia;

  • 作者单位

    Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada College of Chemistry, Beijing Normal University, Beijing 100875, China;

    Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号