Heme protein catalysis and the biocoordination chemistry of HNO

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This award in the Chemistry of Life Processes (CLP) program supports work by Professor Patrick Farmer at Baylor University on biological NOx catalysis, with a recent focus on the generation and reactivity of nitroxyl (HNO) adducts of metalloproteins. NOx intermediates are involved in the catalytic cycles of enzymes that control nitrogen-based metabolism in plants and animals. Previous work has identified several distinct steps in reductive pathways, including the formation of metal-bound HNO intermediates. The Farmer lab has demonstrated that many ferrous heme proteins like myoglobin and hemoglobin trap free HNO efficiently to form stable HNO adducts. Like oxymyoglobin, these HNO complexes are low spin d6 and diamagnetic; they have been well characterized by different spectroscopic and analytical techniques, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and X-ray Absorption Spectroscopy (XAS). New projects continue the exploration of the bio-coordination chemistry of HNO, including new "nitroxyl" adducts of non-heme enzymes and model complexes. The enzyme quercetinase which utilizes O2 to chemically modify flavonols, has been shown to turnover in the presence of HNO, generating products that incorporate the atoms of nitroxyl. The combination of classical coordination chemistry, molecular biology and physical characterization techniques provides a wide breadth of training for both graduate and undergraduate students. A departmental NMR instrument will be upgraded for use in outreach to college students from smaller regional colleges through the Advanced Instrumentation Workshop, which hosted 22 students and 8 faculty members from 10 different schools in 2009, the majority from underrepresented groups.The intent of this award is to address mechanistic aspects of metalloprotein reactivity from an inorganic perspective, i.e., the inorganic chemistry that underlies biological nitrogen-based metabolism. As HNO reacts with O2-binding proteins, Professor Farmer and his team hypothesize that it should form stable complexes with metal sites that are known to bind oxygen. This hypothesis has already led to identification of a previously unknown enzymatic reaction. Ultimately, these studies will have implications for the global effects of modern agriculture, based on understanding the chemical basis for the generation of non-carbon greenhouse gases.