EPR and Mössbauer Characterization of Mn and Fe Enzymes, Biomimetic Models, and Intermediates

标题：锰和铁酶的EPR和穆斯堡尔表征，仿生模型，和 中间体的 项目摘要 包括人类在内的许多生物体的生命依赖于小的稳定分子的激活 通过金属蛋白提供选择性和快速的化学转化。我们的目标是让人们 通过研究金属上发生的原子水平变化， 当酶转换它们的底物时，活性位点。这些研究随着调查而增加 相关的仿生复合物，允许研究活化复合物的特定状态， 在化学反应过程中不容易被捕获。快速冷冻淬火技术的结果， 光谱学和密度泛函理论计算将结合起来，以确定新的催化 中间体的预计我们的研究将更好地了解 确定酶促反应的特异性和效率。 拟议的研究将涉及三个具体目标： ·表征一氧化氮还原酶的催化机制。人类拥有防御能力 产生NO的系统，以对抗病原菌的入侵。作为回应，细菌可以 表达清除NORs以保护生物体免受我们防御系统的攻击。知识 NOR机制可能为抑制这些防御反应提供了靶点。 ·用于分子氧和水活化的仿生复合物的表征。酶会分解 O-O键对于断裂C-H键至关重要，而催化双氧键形成的键 是光合作用的关键我们将研究铁和锰的仿生复合物， 追求反应分子状态的目的已经假设，但其存在， 还没被发现 ·硫醇双加氧酶的催化机制的表征。与硫有关的酶- 氧化和转移越来越被认为是潜在的药物开发靶点 抗微生物剂、癌症和炎症的治疗方法。我们将调查元素 酶反应机制中的步骤，提供生物生产的第一步 无机硫酸盐亚牛磺酸和牛磺酸

Title: EPR and Mössbauer Characterization of Mn and Fe Enzymes, Biomimetic Models, and Intermediates. Project Abstract Life for many organisms, including humans, depends on the activation of small stable molecules by metalloproteins to provide selective and rapid chemical transformations. Our goal is to give insight into how specific enzymes function through studies of the atomic level changes that occur at the metal active site as the enzymes turn over their substrate. These studies are augmented with investigations of relevant biomimetic complexes that allow specific states of activated complexes to be studied that cannot be easily trapped during chemical reactions. The results of rapid freeze quench techniques, spectroscopy, and density functional theory calculations will be combined to identify new catalytic intermediates. It is anticipated that our studies will provide a better understanding of the factors that determine the specificity and efficiency of enzymatic reactions. Three specific aims will be addressed by the proposed studies: • Characterization of the catalytic mechanism of nitric oxide reductases. Humans possess defense systems that produce NO to combat the invasion of pathogenic bacteria. In response, bacteria can express scavenging NORs to protect the organisms against our defense systems. Knowledge of the NOR mechanism may provide targets for suppressing these defensive responses. • Characterization of biomimetic complexes for dioxygen and water activation. Enzymes that break O-O bonds are critical for cleaving C-H bonds while those that catalyze dioxygen bond formation are key to photosynthesis. We will investigate biomimetic complexes of iron and manganese with the aim of pursuing reactive molecular states that have been postulated but whose existence has as yet eluded detection. • Characterization of the catalytic mechanism of thiol dioxygenases. Enzymes involved in sulfur- oxidation and transfer are increasingly being recognized as potential drug targets for development of antimicrobials, therapies for cancer, and inflammatory disease. We will investigate the elemental steps in the reaction mechanisms of enzymes that provide the first step in the biological production of inorganic sulfate, hypotaurine, and taurine.