Substrate Modification at Redox Active Copper Centers

氧化还原活性铜中心的基材改性

• 批准号: 6709365
• 负责人: Jason M Shearer
• 金额: $ 2.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6709365
• 关键词: active sites; chemical models; chemical substitution; copper; dopamine beta monooxygenase; enzyme activity; enzyme substrate; hydrocarbons; hydroxylation; metalloenzyme; oxidation reduction reaction; oxygenases; postdoctoral investigator; synthetic enzyme

DESCRIPTION (provided by applicant): The research outlined in this proposal is aimed at understanding the fundamental chemistry taking place at the copper-centers of Dopamine Beta Hydroxylase and Peptideglycine alpha Hydroxylating Monooxygenase. Both enzymes contain two structurally isolated and spectroscopically distinct copper centers and catalyze the hydroxylation of hydrocarbon substrates using dioxygen as the sole oxidant. Synthetic models will be made to mimic both of these centers. One series of models that will be prepared is a mononuctear copper center aimed at mimicking the reactive properties of the metal-center that is proposed to be the site where hydrocarbon hydroxylation takes place through a supposed CuII-hydroperoxo intermediate. Studies will be performed to elucidate the mechanism of substrate oxidation by this copper-center mimic. Dinuclear models will be made containing mimics for both copper-cites, Studies with the dinuclear complexes will be aimed at understanding how the two centers work in concert to generate the CuII-hydroperoxo species.

描述（由申请人提供）：该提案中概述的研究旨在了解在多巴胺β羟化酶和肽甘氨酸α-羟基羟基氧酶的铜中心发生的基本化学。这两种酶均包含两个结构分离的和光谱上不同的铜中心，并使用二恶英作为唯一的氧化剂催化烃底物的羟基化。合成模型将用于模仿这两个中心。一系列将准备的模型是一个单核铜中心，旨在模仿金属中心的反应性能，该中心的反应性特性是通过假定的CuII-Hydroperoxo中间体进行碳氢化合物羟基化的位置。将进行研究以阐明该铜中心模拟物的底物氧化机理。将制作含有两个铜燃料的模拟物的双核模型，对双核络合物的研究将旨在了解两个中心如何协同工作以生成Cuii-Hydroperoxo物种。