RUI: Magnetic circular dichroism of dicobalt(II) enzymes

通过这一奖项，生命过程化学计划资助米德尔伯里学院的詹姆斯·拉拉比教授使用磁圆二色谱(MCD)对金属水解酶进行研究。将研究的五种金属水解酶与当前社会重要的健康和医疗问题有关。这些酶的活性部位在化学上是相似的；具体地说，它们包括由羧酸盐和水(或氢氧化物)配体桥联的两个金属离子。这些酶是由Larrabee教授的研究小组以Co(II)形式研究的，这种形式提供了特别强的MCD信号。研究的目的之一是提高我们对底物如何与活性中心中的金属离子相互作用的理解。通过MCD光谱监测作为抑制剂的底物类似物与酶结合所引起的金属环境的变化，并提供对酶机制的洞察。第二个目标是发现活性部位的哪些氨基酸残基对这些酶的功能是重要的。了解酶如何发挥作用具有科学意义，对于与疾病相关的生物学过程中涉及的酶，它可能有助于疾病的诊断和治疗。Larrabee教授研究的酶属于后一类，拟议的研究旨在促进对其机制的理解。建议中描述的光谱和量热研究将检查酶活性位置的金属结合和电子结构。还将研究与作为抑制剂的底物或底物类似物相互作用引起的活性部位的变化。这项拟议的研究是由米德尔伯里学院的本科生进行的。众所周知，像米德尔伯里大学本科生那样的研究经历会鼓励学生进一步接受科学教育，追求科学事业。

Through this award, the Chemistry of Life Processes Program is funding Professor James Larrabee at Middlebury College to carry out studies of metallohydrolases using magnetic circular dichroism (MCD) spectroscopy. The five metallohydrolases that will be studied are related to health and medical problems of current importance for the society. The active sites of these enzymes are chemically similar; specifically they include two metal ions bridged by carboxylate and water (or hydroxide) ligands. The enzymes are studied by the research group of Professor Larrabee in the Co(II) form, which provides an especially strong MCD signal. One aim of the research is to improve our understanding of how substrates interact with the metal ions in the active sites. Changes in the metal environment caused by the binding of substrate analogues that function as inhibitors to the enzymes are monitored by MCD spectroscopy and provide insight into the mechanism of the enzyme. A second aim is to discover which amino acid residues in the active site are important for the function of these enzymes. Understanding how enzymes function is of scientific interest and, in the case of enzymes implicated in disease-related biological processes, it may help with the diagnosis and treatment of the diseases. The enzymes studied by Professor Larrabee pertain to the latter category and the proposed studies are designed to advance the understanding of their mechanism. The spectroscopic and calorimetric studies described in the proposal will examine the metal binding and the electronic structure of the active sites of the enzymes. Changes in the active sites induced by interaction with substrate or substrate analogs that function as inhibitors will also be studied. The proposed research is conducted at Middlebury College by undergraduate students. Research experiences such as those undertaken by the Middlebury undergraduates are known to encourage the students to further their science education and to pursue careers in science.