ACTIVITY MODULATION OF PROTEIN KINASE AND PHOSPHATASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 磷酸化/去磷酸化是生物体中发生的最重要的化学反应，是调控由细胞外效应物引发的多种生物事件的基础。我们的项目包括确定两种蛋白激酶的晶体结构，AceK(也是一种蛋白磷酸酶)和ETK，以及一种蛋白磷酸酶，钙调神经磷酸酶。AceK同时具有激酶和磷酸酶的活性，为了研究AceK的活性转换和调控机制，需要解决AceK的激酶和磷酸酶构象以及AceK-ICDH的复合体结构。全长膜ETK、其突变体及其与底物UGD的络合物的结构将被确定。对于钙调神经磷酸酶，它是真核生物中钙调素激活的信号中枢控制器，我们创建了一个融合结构(称为CBA)来帮助确定钙调蛋白-钙调神经磷酸酶复合体的结构，这将代表钙调蛋白复合体中具有完整底物的结构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Phosphorylation/dephosphorylation is the most crucial chemical reaction taking place in living organisms, which is the basis for the regulatory control of many diverse biological events triggered by extracellular effectors. Our project involves the determination of the crystal structures of two protein kinases, AceK (also a protein phosphatase) and Etk, and a protein phosphatase, calcineurin. For AceK, which possesses both kinase and phosphatase activities, the kinase and phosphatase conformations of AceK, as well as AceK-ICDH complex structures will be solved for investigating the AceK activity switch and regulatory mechanism. The structures of full length membrane Etk, its mutants, and its complex with substrate Ugd will be determined. For calcineurin, which is a calmodulin-activated central controller of signaling in eukaryotes, we have created a fusion construct (known as CBA) to facilitate the structure determination of calmodulin-calcineurin complex, which would represent a structure of calmodulin in complex with an intact substrate.