Mechanistic studies on a bimetallic aminopeptidase

双金属氨肽酶的机理研究

• 批准号: 6791373
• 负责人: GABRIEL S BRANDT
• 金额: $ 4.3万
• 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/6791373
• 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博士计划在Brandeis大学进行的博士后培训研究将是对氨基肽酶(AAP)催化活性的结构性酶学研究。AAP是一类生理和临床上重要的酶的原型，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特征：两个金属离子通过桥联配体连接在一起。AAP的晶体结构已经确定，其他几十种桥联双金属酶的结构也得到了解决，但这两种金属离子如何协同催化仍是未知的。为了解决这个重要问题，勃兰特博士提出了一系列的结晶学和生物化学研究。尽管该项目建立在他研究生工作的某些方面，但它代表着一个重大的扩展，因为它不仅包括学习蛋白质结晶学，还包括学习时间分辨结晶学。因此，该项目是一线研究和培训的理想组合。