SYNTHETIC APPROACHES FOR MODELLING METAL-OXO PROTEINS

金属氧化蛋白建模的合成方法

• 批准号: 3295418
• 负责人: LAWRENCE QUE
• 金额: $ 15.38万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3295418
• 关键词: Mossbauer spectrometry; Raman spectrometry; X ray crystallography; acid phosphatase; active sites; catalase; chemical binding; chemical models; cytochrome oxidase; electron spin resonance spectroscopy; enzyme mechanism; ferritin; hemerythrin; hydrolysis; iron; ligands; metal complex; metalloenzyme; metalloproteins; nuclear magnetic resonance spectroscopy; oxidoreductase; oxygenases; peptide chemical synthesis; peroxides; protein structure function; spectrometry; synthetic protein

Proteins with active sites consisting of metal centers bridged by oxo or hydroxo groups comprise a new subclass of metalloproteins. This class includes proteins that perform a variety of functions in biology-- dioxygen transport (hemerythrin), the conversion of ribonucleotides to deoxyribonucleotides (ribonucleotide reductase), phosphate ester hydrolysis (purple acid phosphatases), iron storage (ferritin), water oxidation (oxygen evolving complex of Photosystem II), disproportionation of peroxide (Mn-catalase), oxygen utilization (cytochrome c oxidase), and oxygen activation (methane monooxygenase). We propose to model the structures, spectroscopic properties, and reactivities of such sites using tripodal ligands to form (mu-oxo) or (mu-hydroxo) dimetal complexes and binucleating ligands with phenoxo or aloxo groups designed to bridge metal centers. Aspects to be modeled include dioxygen binding (hemerythrin and cytochrome oxidase), oxygen activation (methane monooxygenase and ribonucleotide reductase), mixed-valent states (hemerythrin, purple acid phosphatase, methane monooxygenase), integer spin states (methane monooxygenase, ribonucleotide reductase, cytochrome oxidase), and phosphate binding and phosphate ester hydrolysis in the purple acid phosphatases. The synthetic complexes will be characterized by x-ray crystallography when possible and by a variety of spectroscopic techniques such as NMR, EPR, UV- vis-NIR, Raman, Mossbauer, magnetism, and EXAFS. Peroxide (and dioxygen) complexes will be studied for their ability to oxygenate or oxidize substrates with an emphasis of obtaining mechanistic insight. Mixed-valent complexes will be investigated with regard to their electron delocalization and spin coupling properties. We will also exploit our ability to synthesize heterobimetallic complexes to investigate spin-spin interactions involving Fe(III) or Fe(II) that engender novel EPR and magnetic properties.

蛋白质具有活性位点的蛋白质，由oxo桥接的金属中心组成 羟基组成了金属蛋白的新子类。 这个课 包括在生物学中执行多种功能的蛋白质 - 二氧化物 运输（hemerythrin），核糖核苷酸的转化为 脱氧核糖核苷酸（核糖核苷酸还原酶），磷酸酯水解 （紫色磷酸酶），铁储存（铁蛋白），水氧化 （光系统II的氧气复合物II），过氧化 （Mn-catalase），氧利用（细胞色素C氧化酶）和氧气 活化（甲烷单加氧酶）。 我们建议建模结构， 使用三座 形成的配体（Mu-oxo）或（Mu-Hydroxo）二核复合物和双核 配有苯氧杆菌或α基团的配体旨在桥接金属中心。 要建模的方面包括二氧化物结合（helemerthrin和细胞色素 氧化酶），氧气活化（甲烷单加氧酶和核糖核苷酸 还原酶），混合态态（hegerthin，紫色磷酸酶， 甲烷单氧酶），整数自旋状态（甲烷单加氧酶， 核糖核苷酸还原酶，细胞色素氧化酶）和磷酸盐结合和 紫色磷酸酶中的磷酸酯水解。 合成复合物将以X射线晶体学为特征 可能并通过多种光谱技术，例如NMR，EPR，UV- Vis-Nir，Raman，Mossbauer，Magnetism和Exafs。 过氧化物（和二氧化物） 将研究复合物的氧化或氧化能力 底物强调获得机械洞察力。 混合价值 复合物将针对其电子离域化进行研究 和自旋耦合属性。 我们还将利用我们的能力 合成杂粒金属络合物以研究自旋旋转相互作用 涉及Fe（iii）或Fe（II）引起新颖的EPR和磁性 特性。