Synthetic Modeling of Copper Protein Active Sites

铜蛋白活性位点的综合建模

• 批准号: 7108007
• 负责人: WILLIAM B Tolman
• 金额: $ 30.44万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7108007
• 关键词: Raman spectrometry; active sites; chemical models; chemical synthesis; copper; cytochrome oxidase; electron spin resonance spectroscopy; electron transport; hydrogen bond; metalloproteins; model design /development; nitric oxide; nitrous oxide; oxygen; oxygenases

DESCRIPTION (provided by applicant): Proteins that contain copper ions in their active sites represent a large and functionally significant class of metallobiomolecules that play important roles in a wide range of life processes. The functional diversity of copper proteins is matched by variability in active site geometric, electronic structural, and spectroscopic features. A molecular level understanding of structure/function relationships is desirable, but despite extensive research efforts many issues remain unresolved regarding the detailed mechanisms of action and underlying chemistry of copper protein active sites. The aim of the proposed research is to obtain essential chemical insights into copper protein structure and function and to develop novel and fundamentally significant copper chemistry through the synthetic modeling approach, wherein low molecular weight complexes designed to replicate metalloprotein active site properties are characterized and their reactivity studied. The specific aims of the proposed research are to: 1. Understand the interrelationships of the variable structures and redox behaviors of type 1 copper electron transfer sites found in numerous metalloproteins. Perturbations of copper-thiolate complex properties and electron transfer kinetics of ruthenium and/or rhenium/copper-thiolate assemblies will be examined. 2. Obtain fundamental insight into dioxygen activation by monocopper sites in biologically important proteins such as dopamine beta-monooxygenase and galactose oxidase through studies of the O2 reactivity of copper complexes of hindered bidentate N-donor ligands, phenolate chelates, and ligands with attached remote oxidants like those operative in catalysis by copper enzymes. 3. Investigate dioxgyen activation by the tricopper active sites of the ubiquitous and biologically significant multicopper oxidases by using a novel stepwise synthetic strategy involving the reaction of 1:1 Cu/O2 species with dicopper complexes. 4. Understand the underlying chemistry of the novel (mu-sulfido)tetracopper active site of nitrous oxide reductase, an important participant in the global nitrogen cycle. Parallel studies will be performed of various mono- and disulfido-bridged dicopper complexes and of specifically designed tetracopper clusters.

描述（由申请人提供）：在其活性位点中包含铜离子的蛋白质代表了在广泛的寿命过程中起重要作用的大型且功能意义的金属生物分子。铜蛋白的功能多样性与活性位点几何，电子结构和光谱特征的变异性相匹配。对于结构/功能关系的分子水平的理解是可取的，但是尽管进行了广泛的研究工作，许多问题仍未解决，尚未解决铜蛋白活性位点的详细作用机理和基础化学。拟议研究的目的是通过合成建模方法获得对铜蛋白结构和功能的基本化学见解，并通过合成建模方法开发新颖和根本的铜化学，其中旨在复制金属蛋白活性位点特性的低分子量复合物被表征并研究了其反应性。拟议研究的具体目的是：1。了解可变结构的相互关系和1型铜电子转移位点的氧化还原行为的相互关系。将检查唯一的硫醇含量复杂性能和氟苯和/或rhenium/或rhenium/铜 - 硫醇酸盐组件的电子转移动力学的扰动。 2。通过研究由抑制型N-Donor配体的铜复合物的O2反应性的研究，通过研究均具有远程氧化剂（如均匀的氧化剂），从而获得了生物学上重要的蛋白质（例如多巴胺β-单加氧酶和半乳糖氧化酶）的基本见解。 3。通过使用一种新型的逐步合成策略，研究了无处不在和生物学上具有重要多功能氧化酶的三角孔活性位点的激活，涉及1：1 cu/o2物种与二氧化碳复合物的反应。 4。了解一氧化二氮还原酶的新颖的四脂蛋白活性位点，这是全球氮循环的重要参与者。平行研究将对各种单硫桥式的双子型配合物以及专门设计的四翼簇簇进行。