The long-term goal of this research is to elucidate the reaction mechanisms of NO reduction that occur at heme and non-heme diiron centers of bacterial metalloenzymes. Our studies will focus on two enzymatic systems and related bioengineered or synthetic models: 1) NO-detoxifying flavodiiron proteins (FDPs) and 2) denitrifying NO reductases (denNORs). All of the proteins within these two families are known to reduce NO to the unreactive N2O product, but they do so with wide variation in efficiency and protein matrix structure. Although several of these proteins have been characterized by X-ray crystallography, the initial steps of NO binding, iron-nitrosyl reduction, and how these catalytic events differ between systems are not well understood. The coupling of resonance Raman, FTIR, and EPR spectroscopies with rapid-freeze-quench analyses provides unique capabilities to define NO-binding geometries at diiron clusters and to follow the N-N bond formation, N-O bond cleavage, and protonation steps that must take place to convert two NO molecules to N2O and H2O. Studying a diverse group of native enzymes and models will allow us to compare and contrast structural information on iron-nitrosyl intermediates and the efficiency of the reductive and proton transfer steps of this reaction.

Public Health Relevance

A better understanding of microbial NO reductases is highly desirable since these enzymatic reactions lead to microorganisms'resistance to the mammalian immune response. Furthermore, there are no human orthologs to these microbial enzymes;they represent potential targets for new drugs.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Special Emphasis Panel (ZRG1-BCMB-B (02))
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Anderson, Vernon
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Oregon Health and Science University
Schools of Medicine
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Bhagi-Damodaran, Ambika; Reed, Julian H; Zhu, Qianhong et al. (2018) Heme redox potentials hold the key to reactivity differences between nitric oxide reductase and heme-copper oxidase. Proc Natl Acad Sci U S A 115:6195-6200
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