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

项目总结 金属酶在整个人类健康中起着至关重要的作用，并控制着氧气(O2)和 一氧化氮(NO)。病原生物体依靠血红素和非血红素含铁蛋白来对抗 人体免疫反应和在高浓度的活性氧和氮中生存 物种(ROS/RNS)。酩悦·洛科兹实验室结合了经典的生化技术，共振拉曼 (RR)、FTIR和EPR光谱与时间分辨技术用于探测微生物酶系统 以X射线结晶学为特征，但催化策略仍鲜为人知或完全 未知。在这个项目中，一种新的分枝杆菌双铁蛋白的最新晶体结构上调 巨噬细胞感染在表现出独特的结构特征和对 RNS在生物学或无机化学中从未见过。

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.