ACTIVITY MODULATION OF PROTEIN KINASE AND PHOSPHATASE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 磷酸化/去磷酸化是生物体中最重要的化学反应，是细胞外效应物引发的多种生物学事件调控的基础。我们的项目涉及两种蛋白激酶AceK（也是一种蛋白磷酸酶）和Etk以及一种蛋白磷酸酶钙调磷酸酶的晶体结构的测定。对于同时具有激酶和磷酸酶活性的AceK，将解决AceK的激酶和磷酸酶构象以及AceK-ICDH复合物结构，以研究AceK活性开关和调节机制。将确定全长膜Etk、其突变体及其与底物Ugd的复合物的结构。 对于钙调磷酸酶，这是一个钙调蛋白激活的中央控制器的信号在真核生物中，我们已经创建了一个融合构建体（称为CBA），以促进钙调蛋白-钙调磷酸酶复合物的结构测定，这将代表一个完整的底物复合物的钙调蛋白的结构。

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.