RUI: Magnetic circular dichroism of dicobalt(II) enzymes

通过这个奖项，生命过程计划的化学正在资助米德尔伯里学院的James Larrabee教授使用磁性圆二色性（MCD）光谱进行金属水解酶的研究。将要研究的五种金属水解酶与当前社会重要的健康和医学问题有关。这些酶的活性位点在化学上是相似的;具体地说，它们包括由羧酸根和水（或氢氧化物）配体桥接的两个金属离子。Larrabee教授的研究小组以Co（II）形式研究了这种酶，这种形式提供了特别强的MCD信号。该研究的目的之一是提高我们对底物如何与活性位点中的金属离子相互作用的理解。通过MCD光谱监测作为酶抑制剂的底物类似物的结合引起的金属环境的变化，并提供对酶机制的深入了解。第二个目标是发现活性位点中的哪些氨基酸残基对这些酶的功能是重要的。了解酶的功能具有科学意义，并且在涉及疾病相关生物过程的酶的情况下，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。该提案中描述的光谱和量热研究将检查金属结合和酶活性位点的电子结构。还将研究与作为抑制剂的底物或底物类似物相互作用诱导的活性位点的变化。拟议中的研究是由米德尔伯里学院的本科生进行的。研究经验，如由明德大学本科生进行的，以鼓励学生进一步他们的科学教育和追求科学事业。

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.