Nitric oxide dioxygenase mechanism of the truncated hemoglobin N from Mycobacterium tuberculosis

本项目旨在详细解剖一氧化氮双加氧酶（NOD）反应的截断血红蛋白N（TrHbN）从致病性细菌结核分枝杆菌（Mtb）。这种酶具有将一氧化氮（-NO）解毒为无害的硝酸盐的强大能力，并在氧气（O2）和感染病变中普遍存在的-NO浓度（O2=1-4 µM; -NO = 0.1 - 1 µM）下保护有氧呼吸免受-NO的抑制。TrHbN可能是一个新的潜在的治疗药物靶点。详细的反应机理的见解可能会提供必要的分子基础，定向研究在这个方向上。这些机制的研究也可能是非常感兴趣的那些工作与其他血红素酶催化氧化还原反应（过氧化物酶，过氧化氢酶，前列腺素合成酶，细胞色素P450）。所采用的方法是多学科的，将有助于培养高素质的人才。

This project seeks a detailed dissection of the nitric oxide dioxygenase (NOD) reaction of the truncated hemoglobin N (TrHbN) from the pathogenic bacterium Mycobacterium tuberculosis (Mtb). This enzyme has a potent ability to detoxify nitric oxide (-NO) into the innocuous nitrate and to protect aerobic respiration from the inhibition by -NO under oxygen (O2) and -NO concentrations prevailing in infected lesions (O2=1-4 µM; -NO = 0.1 -1 µM). TrHbN may represent a new potential drug target for therapy. Detailed insights of reaction mechanism may provide the molecular basis necessary to orient research in this direction. These mechanistic studies may also be of great interest to those working with other heme enzymes that catalyze redox reactions (peroxidase, catalase, prostaglandin synthase, cytochrome P450). The approach used is multidisciplinary and will contribute to formation of highly qualified personnel.