CRYSTALLOGRAPHIC ANALYSIS OF MAP KINASES

MAP 激酶的晶体分析

• 批准号: 2701134
• 负责人: ELIZABETH J. GOLDSMITH
• 金额: $ 22.01万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2701134
• 关键词: X ray crystallography; adenosinetriphosphatase; enzyme activity; enzyme substrate complex; gene mutation; hydroxyaminoacid; mitogen activated protein kinase; phosphoproteins; proline; protein structure function; site directed mutagenesis

DESCRIPTION: The long-term goal of this research project is to understand the complex regulatory mechanism of ERK2, a MAP kinase. MAP kinases are important elements of signal transduction pathways initiated by hormones, cytokines, or environmental stress. MAP kinases such as ERK2 are activated after phosphorylation by MAP/ERK kinases (MEKs), which are themselves activated by Ras/Raf proteins following cell stimulation. As such, these enzymes may present useful therapeutic targets. MAP kinases have several interesting properties, including a complex dual phosphorylation regulatory mechanism and a high substrate specificity for hydroxyamino acids that are followed by proline in the target protein's sequence. Few protein kinase systems have been thoroughly investigated and none has crystallographic data for both the inactive and active or phosphorylated forms of the same enzyme.

描述：该研究项目的长期目标是了解 ERK2的复杂调节机制，一种MAP激酶。 地图激酶是 由激素引发的信号转导途径的重要元素， 细胞因子或环境压力。 诸如ERK2之类的MAP激酶被激活 通过MAP/ERK激酶（MEK）磷酸化后，它本身就是 细胞刺激后，由RAS/RAF蛋白激活。 因此，这些 酶可能提出有用的治疗靶标。 地图激酶有几个 有趣的特性，包括复杂的双磷酸化调节 机理和高底物特异性的羟基氨基酸是 然后是靶蛋白序列中的脯氨酸。 很少的蛋白激酶 系统已经进行了彻底的研究，没有一个具有晶体学数据 对于同一酶的非活性和活性或磷酸化形式。