RUI: Magnetic Circular Dichroism of Dicobalt(II) Enzymes and Complexes

该研究奖在CHE部门的无机，生物无机和有机化学计划以及分子和细胞生物科学部门支持由米德尔伯里学院的James Larrabee教授使用磁性圆二色光谱进行金属水解酶的基础研究。研究中的四种酶是甲硫氨酸氨肽酶、金属β-内酰胺酶、甘油磷酸二酯酶和磷酸三酯酶;这些酶都具有由羧酸根和水（或氢氧化物）配体桥接的两个金属离子的共同活性位点结构基序。这些酶以钴（II）形式进行研究。这种方法提供了一个特别强的磁性圆二色信号，用于监测金属环境的变化，因为抑制剂结合到酶。这些变化被用来深入了解酶的机制，预计这是相似的，因为酶的活性位点的结构相似性。这项研究在米德尔伯里学院是由本科生研究助理作为合作者进行的。这种类型的研究经验鼓励本科生追求科学事业，并通过参加研究生院进一步他们的科学教育。该研究奖共支持9名本科生研究助理。了解酶的功能通常对科学很重要;然而，更好地了解这四种酶对社会有潜在的好处。甲氨酰氨基肽酶已被确定为抗血管生成药物的靶酶;因此，抑制剂是治疗实体瘤癌症、动脉硬化和类风湿性关节炎的候选药物。金属β-内酰胺酶水解β-内酰胺，这是细菌对β-内酰胺治疗耐药的主要原因。酯酶水解多种有机磷，在有机磷农药污染的生物修复和有机磷神经性毒剂的解毒方面具有潜在的应用价值。

This research award in the Inorganic, Bioinorganic, and Organometallic Chemistry program of the CHE division and in the Molecular and Cellular Biosciences Division supports work by Professor James Larrabee at Middlebury College to carry out fundamental studies on metallohydrolase enzymes using magnetic circular dichroism spectroscopy. Four enzymes that are in the study are methionine aminopeptidase metallo beta-lactamase, glycerophosphodiesterase, and phosphotriesterase; these enzymes all share the common active site structural motif of two metal ions bridged by carboxylate and water (or hydroxide) ligands. These enzymes are studied in the cobalt(II) form. This approach provides an especially strong magnetic circular dichroism signal that is used to monitor changes in the metal environment as inhibitors are bound to the enzymes. These changes are used to gain insight into the enzyme mechanisms, which are expected to be similar because of the structural similarities of the enzyme active sites.This research study at Middlebury College is conducted by undergraduate research assistants as collaborators. This type of research experience encourages undergraduates to pursue careers in science and to further their science education by attending graduate school. This research award is supporting a total of nine undergraduate research assistants. Understanding how enzymes function is generally important to science; however, a better understanding of these four enzymes has potential benefit to society. Methionine aminopeptidase has been identified as the target enzyme of anti-angiogenesis drugs; therefore, inhibitors are drug candidates to treat solid tumor cancers, arterial sclerosis, and rheumatoid arthritis. Metallo beta-lactamase hydrolyzes beta-lactams, a process which is the major cause of bacterial resistance to beta-lactam therapy. The esterases hydrolyze a number of organophosphates and have potential in bioremediation of organophosphate pesticide contamination and detoxification of organophosphate nerve agents.