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

微生物非血红素二铁蛋白的亚硝化应激和NO解毒反应机制

基本信息

批准号：
10656107
负责人：
PIERRE MOENNE-LOCCOZ
金额：
$ 32.34万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10656107
关键词：
Active Sites Aerobic Binding Biochemical Biochemistry Biological Process Biology Catalysis Complex Conversion disorder Data Detoxification Process Dioxygen Dissociation Drug Metabolic Detoxication Electron Spin Resonance Spectroscopy Equation Exposure to Flavins Goals Health Heme Hemeproteins Hemerythrin Hemoglobin Human Immune response Infection Inorganic Chemistry Investigation Ions Iron Kinetics Ligands Macrophage Metals Molecular Mycobacterium kansasii Mycobacterium tuberculosis Nitrates Nitric Oxide Nitrites Nitrogen Nitrous Oxide Organism Oxidases Oxidation-Reduction Oxidative Stress Oxygen Oxygenases Pathogenicity Pathway interactions Physiological Play Process Proteins Protons Raman Spectrum Analysis Reaction Reactive Nitrogen Species Research Roentgen Rays Role Route Site Site-Directed Mutagenesis Sodium Chloride Spectroscopy, Fourier Transform Infrared Spectrum Analysis Stress Structure Surveys System Techniques Theoretical model Time Tuberculosis Uncertainty X-Ray Crystallography cofactor combat denitrification experimental study metalloenzyme microbial microorganism mycobacterial nitric oxide reductase nitrosative stress novel overexpression response stoichiometry structural determinants

项目摘要

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.

项目摘要金属酶在人类健康中发挥着至关重要的作用，并控制着分子氧（O2）和一氧化氮（NO）。病原生物体依赖于血红素和非血红素含铁蛋白质来对抗人体免疫反应和生存暴露于高浓度的活性氧和氮种（ROS/RNS）。Moënne-Loccoz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探测微生物酶系统其特征在于X射线晶体学，但催化策略仍然知之甚少或完全未知在这个项目中，最近的一个新的分枝杆菌二铁蛋白的晶体结构，巨噬细胞感染在显示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。