Nitrophorins as Multifunctional Heme Enzymes: The Peroxidase Activity

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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.