RUI: Magnetic circular dichroism of dicobalt(II) enzymes

通过该奖项，生命过程化学项目资助米德尔伯里学院的詹姆斯·拉拉比教授使用磁性圆二色性（MCD）光谱进行金属水解酶的研究。将研究的五种金属水解酶与当前社会重要的健康和医学问题有关。这些酶的活性位点在化学上是相似的；具体来说，它们包括两个由羧酸盐和水（或氢氧根）配体桥接的金属离子。Larrabee教授的研究小组研究了Co（II）形式的酶，它提供了一个特别强的MCD信号。这项研究的目的之一是提高我们对底物如何与活性位点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结合引起的金属环境变化，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，在与疾病相关的生物过程有关的酶的情况下，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。提案中描述的光谱和量热研究将检查酶活性位点的金属结合和电子结构。与底物或作为抑制剂的底物类似物相互作用引起的活性位点的变化也将被研究。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，像明德大学本科生所进行的研究经历，可以鼓励学生进一步接受科学教育，并追求科学事业。

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.