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

Mn 和 Fe 酶、仿生模型和中间体的 EPR 和穆斯堡尔表征

基本信息

批准号：
9174637
负责人：
MICHAEL P HENDRICH
金额：
$ 26.61万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9174637
关键词：
Active Sites Address Aerobic Amino Acids Bacteria Biochemical Biochemical Reaction Biological Biology Biomimetics Chemicals Cleaved cell Complex Detection Development Dioxygen Dioxygenases Disease Drug Targeting Environment Enzymes Flavins Freezing Goals Heme Human Hydrogen Bonding Image Inflammatory Inorganic Sulfates Investigation Ions Iron Knowledge Life Location Manganese Metalloproteins Metals Methane hydroxylase Modeling Molecular Monitor Mononuclear Nature Organism Oxidants Oxidoreductase Oxygen Photosynthesis Plant Roots Process Production Proteins Protons Reaction Ribonucleotide Reductase Site Specificity Spectrum Analysis Structure Sulfhydryl Compounds Sulfur System Taurine Techniques Testing Water abstracting antimicrobial cancer therapy chemical reaction cofactor combat density enzyme mechanism hypotaurine improved insight nitric oxide reductase oxidation pathogenic bacteria prevent protonation research study response spectroscopic imaging theories

项目摘要

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.

标题：Mn和Fe酶的EPR和Mössbauer表征，仿生模型以及中间人。项目摘要包括人类在内的许多生物的生命取决于小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。我们的目标是提供见识特定酶通过研究金属的原子水平变化如何发挥作用当酶翻转其底物时，活性位点。这些研究通过调查增强相关的仿生复合物，允许研究活性复合物的特定状态化学反应期间不能轻易捕获。快速冻结技术的结果，光谱和密度功能理论计算将结合起来以鉴定新的催化中间人。可以预料，我们的研究将更好地理解确定酶促反应的特异性和效率。拟议的研究将解决三个具体目标： •一氧化氮减少的催化机理的表征。人类拥有防御产生不打击病原细菌侵袭的系统。作为回应，细菌可以明确清除NORS，以保护生物体免受我们的防御系统的影响。了解也不能提供抑制这些防御反应的目标。 •二氧化物和水活化的仿生复合物的表征。破裂的酶 O-O键对于裂解C-H键，而催化二氧键形成的键至关重要是光合作用的关键。我们将研究铁和锰的仿生复合物追求已假定的反应性分子状态但其存在的目的尚未发现检测。 •表征硫醇二氧酶的催化机理。参与硫的酶氧化和转移越来越被认为是潜在的发育药物靶标抗菌素，癌症疗法和炎症性疾病。我们将研究元素酶的反应机理的步骤，该酶提供了生物生产的第一步无机硫酸盐，午后和牛磺酸的含量。