ANALYSIS OF EUKARYOTIC PROTEIN KINASES AND PHOSPHO-REGULATORY SYSTEMS

真核蛋白激酶和磷酸调节系统的分析

• 批准号: 8169230
• 负责人: FRANK SICHERI
• 金额: $ 1.05万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169230
• 关键词: Cellular biology; Computer Retrieval of Information on Scientific Projects Database; Disease; Event; Functional disorder; Funding; Goals; Grant; Human Genome; Institution; Learning; Mutation; Pharmaceutical Preparations; Phosphorylation; Phosphotransferases; Protein Kinase; Proteins; Research; Research Personnel; Resources; Source; Stream; Structure; System; Therapeutic; United States National Institutes of Health; Viral; base; human disease; inorganic phosphate; macromolecular assembly; novel; small molecule; stem

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. The human genome encodes just over 500 protein kinases. These kinases catalyze the transfer of the gamma phosphate of ATP to a specific hydoxyl group onto their target protein. This phosphorylation event can induce conformational changes or promote the formation of macromolecular assemblies. Aberrant protein kinase function arising from mutation or viral subversion mechanisms gives rise to cellular dysfunctions that underlie numerous human diseases. The ability to counteract aberrant protein kinase function through the use of small molecule therapeutics has validated the protein kinase as a drugable target. The pervasiveness of protein kinases as regulators of cellular biology, stems from a plasticity of structure that allows for the diversification of catalytic switching and substrate recognition mechanisms. To date only a small fraction of eukaryotic protein kinases have been structurally characterized. In my lab, we are seeking to uncover the structural basis for novel catalytic switching, substrate recognition and down-stream phospho-regulatory mechanisms. Our long-term goal is to make use of what we learn about protein kinases and phospho-regulatory systems to develop drugs to treat disease.

这个子项目是许多研究子项目中的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 人类基因组编码超过500种蛋白激酶。 这些激酶催化ATP的γ磷酸转移到其靶蛋白上的特定羟基基团。 这种磷酸化事件可以诱导构象变化或促进大分子组装体的形成。 由突变或病毒颠覆机制引起的异常蛋白激酶功能引起细胞功能障碍，这是许多人类疾病的基础。 通过使用小分子治疗剂抵消异常蛋白激酶功能的能力已经验证了蛋白激酶作为可药物化靶点。 蛋白激酶作为细胞生物学调节剂的普遍性源于结构的可塑性，其允许催化转换和底物识别机制的多样化。迄今为止，只有一小部分真核蛋白激酶的结构特征。 在我的实验室，我们正在寻求揭示新的催化开关，底物识别和下游磷酸调控机制的结构基础。我们的长期目标是利用我们对蛋白激酶和磷酸调节系统的了解来开发治疗疾病的药物。