Mechanistic studies on a bimetallic aminopeptidase

双金属氨肽酶的机理研究

• 批准号: 6691527
• 负责人: GABRIEL S BRANDT
• 金额: $ 3.97万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691527
• 关键词: X ray crystallography; aminopeptidase; binding sites; carboxylate; catalyst; enzyme structure; hydroxides; ligands; metalloenzyme; metals; site directed mutagenesis

DESCRIPTION (provided by applicant): The research that Dr. Brandt proposes to conduct at Brandeis University for his postdoctoral training shall be a structural enzymology investigation of the catalytic activity of the enzyme aminopeptidase (AAP). AAP is the prototype of a class of physiologically and clinically important enzymes, proteins ranging from DNA polymerase to methane monooxygenase. All of these enzymes share a common catalytic feature: two metal ions connected by a bridging ligand. The crystal structure of AAP has been determined, and dozens of other bridged bimetalloenzymes have also had their structures solved, but how the two metal ions cooperate in catalysis is still unknown. Dr. Brandt has proposed a series of crystallographic and biochemical studies to address this important question. Although the project builds on certain aspects of his graduate work, it represents a significant extension, because it includes learning not only protein crystallography, but also time-resolved crystallography. The project thus represents an ideal mix of front-line research and training.

描述（由申请人提供）：Brandt博士建议在Brandeis大学进行博士后培训的研究将是对酶氨肽酶（AAP）催化活性的结构酶学研究。AAP是一类生理和临床上重要的酶的原型，其蛋白质范围从DNA聚合酶到甲烷单加氧酶。所有这些酶都有一个共同的催化功能：两个金属离子通过桥连配体连接。AAP的晶体结构已经确定，其他几十种桥连双金属酶的结构也已经解决，但这两种金属离子如何在催化中合作仍然是未知的。勃兰特博士提出了一系列晶体学和生物化学研究来解决这个重要问题。虽然该项目建立在他的研究生工作的某些方面，但它代表了一个重要的扩展，因为它不仅包括学习蛋白质晶体学，还包括时间分辨晶体学。因此，该项目是一线研究和培训的理想结合。