Nitrosative stress and NO detoxifying reaction mechanisms in microbial nonheme diiron proteins

Oregon Health & Science University, Portland OR

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Abstract

PROJECT SUMMARY Metalloenzymes play crucial roles throughout human health and govern the biochemistry of dioxygen (O2) and nitric oxide (NO). Pathogenic organisms depend on heme and nonheme iron-containing proteins to counter the human immune response and to survive exposure to high concentrations of reactive oxygen and nitrogen species (ROS/RNS). The Moënne-Loccoz Lab combines classic biochemical techniques, resonance Raman (RR), FTIR, and EPR spectroscopies with time-resolved techniques to probe microbial enzymatic systems characterized by X-ray crystallography, but with catalytic strategies that remain poorly understood or totally unknown. In this project, a recent crystal structure of a novel mycobacterial diiron protein upregulated upon macrophage infection is targeted for investigation after showing unique structural features and reactivity toward RNS never seen before in biology or inorganic chemistry.