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.

具有由氧桥桥接的金属中心组成的活性位点的蛋白质 羟基构成金属蛋白的一个新亚类。 本班 包括在生物学中执行多种功能的蛋白质——双氧 运输（血红蛋白），将核糖核苷酸转化为 脱氧核糖核苷酸（核糖核苷酸还原酶），磷酸酯水解 （紫色酸性磷酸酶）、铁储存（铁蛋白）、水氧化 （光系统 II 的放氧复合物），过氧化物歧化 （锰过氧化氢酶）、氧利用率（细胞色素 C 氧化酶）和氧 活化（甲烷单加氧酶）。 我们建议对结构进行建模， 使用三脚架分析此类位点的光谱特性和反应性 配体形成（mu-oxo）或（mu-Hydroxo）双金属配合物并双核 具有苯氧基或铝氧基的配体，旨在桥接金属中心。 要建模的方面包括双氧结合（血红蛋白和细胞色素 氧化酶），氧活化（甲烷单加氧酶和核糖核苷酸 还原酶），混合价态（血红蛋白，紫色酸性磷酸酶， 甲烷单加氧酶），整数自旋态（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 磷酸酯在紫色酸性磷酸酶中水解。 当以下情况时，合成配合物将通过 X 射线晶体学进行表征： 可能并通过各种光谱技术，如 NMR、EPR、UV- vis-NIR、拉曼、穆斯堡尔、磁性和 EXAFS。 过氧化物（和双氧） 将研究复合物的氧化或氧化能力 基底，重点是获得机械洞察力。 混合价 将研究配合物的电子离域性 和自旋耦合特性。 我们还将利用我们的能力 合成异双金属配合物以研究自旋-自旋相互作用 涉及 Fe(III) 或 Fe(II) 产生新颖的 ​​EPR 和磁性 特性。