Nitrophorins as Multifunctional Heme Enzymes: The Peroxidase Activity

硝基钙蛋白作为多功能血红素酶：过氧化物酶活性

• 批准号: 0809591
• 负责人: Frances Ann Walker
• 金额: $ 49.5万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0809591&HistoricalAwards=false
• 关键词: Nitrophorins; Multifunctional; Heme; Enzymes; Peroxidase

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor F. Ann Walker at the University of Arizona to probe the peroxidase activity of the nitrophorins (NPs). These ferriheme proteins, from the saliva of the blood-sucking insect Rhodnius prolixus, are known to sequester NO in the salivary glands and release it into the tissues of the victim during a bite. Preliminary findings have shown that these proteins also react with hydrogen peroxide or peroxyacetic acid (PAA) to oxidize typical substrates of peroxidase enzymes, as well as the important biological effector norepinephrine. The high-valent intermediate known as Compound I is formed after rapid mixing of H2O2 or PAA with NP. Two forms of Compound I are seen at different pH values; at high pH the typical Compound I spectrum is observed, while at low pH a different signal, novel for peroxidase enzymes, but previously seen in model heme complexes, is observed. The factors that cause the appearance of each of these signals, their disappearance to form tyrosyl radicals of the protein, and their subsequent reactivity with organic substrates, will be investigated in this project. A course on peroxidase and oxygenase enzymes will be developed and offered to undergraduate and graduate students in Chemistry, Biochemistry and Pharmaceutical Chemistry at the University of Arizona, and the course materials will be made available to others on the WWW.Peroxides and their oxidation reactions are important in chemical and biological systems and in industrial settings. The mechanisms of hydrogen peroxide (and organic peracid) reaction with transition metals are relevant to large scale chemistry and biochemistry, as well as to the reactions that produce deleterious Reactive Oxygen Species (ROS) in plants and animals. Investigation of the high valent reactivity of the novel ferriheme enzymes to be studied will provide insight into the factors that stabilize each of the high valent Compound I species and their subsequent reactivity with organic substrates.

无机化学、生物无机化学和金属有机化学项目的这一奖项支持了亚利桑那大学F·安·沃克教授探索硝基酚(NP)的过氧化物酶活性的工作。这些从吸血昆虫Rhodnius prolixus的唾液中提取的铁血红素蛋白，已知能将NO隔离在唾液腺中，并在被咬时将其释放到受害者的组织中。初步研究结果表明，这些蛋白质还与过氧化氢或过氧乙酸(PAA)反应，氧化典型的过氧化物酶底物，以及重要的生物效应物去甲肾上腺素。被称为化合物I的高价中间体是在过氧化氢或PAA与NP快速混合后形成的。在不同的pH值下可以看到两种形式的化合物I；在高pH下观察到典型的化合物I光谱，而在低pH下观察到不同的信号，这是过氧化物酶的新信号，但以前在模型血红素络合物中看到。在这个项目中，将研究导致这些信号出现的因素，它们消失以形成蛋白质的酪氨酸自由基，以及它们随后与有机底物的反应。亚利桑那大学将开发一门关于过氧化物酶和加氧酶的课程，并向化学、生物化学和药物化学的本科生和研究生提供课程材料，课程材料将提供给WWW上的其他人。过氧化物酶及其氧化反应在化学和生物系统以及工业环境中非常重要。过氧化氢(和有机过氧酸)与过渡金属的反应机理与大规模化学和生物化学有关，也与在动植物中产生有害的活性氧(ROS)的反应有关。对将要研究的新型铁血红素酶的高价反应性的研究将有助于深入了解稳定每个高价化合物I物种的因素以及它们随后与有机底物的反应活性。