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

标题：锰和铁酶的EPR和穆斯堡尔特性，仿生模型，和 中间体。 项目摘要 包括人类在内的许多生物体的生命依赖于稳定的小分子的激活 通过金属蛋白提供选择性和快速的化学转化。我们的目标是提供洞察力 通过研究发生在金属上的原子水平变化来研究特定的酶是如何发挥作用的 当酶翻转它们的底物时，活性部位。这些研究以调查为补充。 相关仿生复合体，允许研究激活的复合体的特定状态， 在化学反应过程中不易被捕获。快速冷冻淬火技术的结果， 光谱和密度泛函理论计算将结合在一起，以确定新的催化剂 中间体。预计我们的研究将使我们更好地了解 确定酶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 产生一氧化氮以对抗病原菌入侵的系统。作为回应，细菌可以 快速清除NORs以保护生物体免受我们的防御系统的攻击。了解以下内容 NOR机制可能会为抑制这些防御性反应提供靶子。 ·用于氧气和水活化的仿生复合体的特征。分解的酶 O-O键是裂解C-H键的关键，而那些催化形成氧键的键 是光合作用的关键。我们将研究铁和锰的仿生络合物 追求已被假设但其存在的反应性分子状态的目标 到目前为止还没有被发现。 ·表征硫醇双加氧酶的催化机理。与硫磺有关的酶- 氧化和转移日益被认为是潜在的药物开发目标 包括抗菌药、癌症治疗和炎症性疾病。我们将对元素进行调查 在生物生产中提供第一步的酶的反应机制中的步骤 由无机硫酸盐、次牛磺酸和牛磺酸组成。

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.