ACTIVITY MODULATION OF PROTEIN KINASE AND PHOSPHATASE

蛋白激酶和磷酸酶的活性调节

• 批准号: 8170287
• 负责人: Jialin Charles Zheng
• 金额: $ 0.07万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170287
• 关键词: Biological; Calcineurin; Calmodulin; Complex; Computer Retrieval of Information on Scientific Projects Database; Eukaryota; Event; Funding; Grant; Institution; Length; Life; Membrane; Molecular Conformation; Organism; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Protein Dephosphorylation; Protein Kinase; Protein phosphatase; Research; Research Personnel; Resources; Signal Transduction; Source; Structure; United States National Institutes of Health; base; chemical reaction; extracellular; mutant

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 磷酸化/去磷酸化是生物体中最关键的化学反应，这是对受细胞外效应子触发的许多不同生物事件的调节控制的基础。我们的项目涉及确定两种蛋白激酶的晶体结构，即ACEK（也是蛋白质磷酸酶）和ETK，以及一个蛋白质磷酸酶钙调蛋白。对于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活性转换和调节机制。将确定全长膜ETK，其突变体及其与底物UGD的复合物的结构。 对于钙调蛋白是真核生物中信号传导的钙调蛋白激活的中心控制器，我们创建了一种融合构建体（称为CBA），以促进钙调蛋白 - 钙调蛋白络合物的结构测定，这将代表具有完整底物的复合物中钙调蛋白的结构。