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

本项目旨在详细剖析来自致病菌结核分枝杆菌(Mtb)的截短血红蛋白N(TrHbN)的一氧化氮双加氧酶(NOD)反应。这种酶有很强的能力将一氧化氮(-NO)解毒成无毒的硝酸盐，并保护有氧呼吸不受-NO在氧气(O2)下和感染皮损中普遍存在的-NO浓度(O2=1-4微米；-NO=0.1-1微米)的抑制。TrHbN可能是治疗的一个新的潜在药物靶点。对反应机理的详细了解可能会为这一方向的研究提供必要的分子基础。这些机理研究也可能对那些使用其他催化氧化还原反应的血红素酶(过氧化物酶、过氧化氢酶、前列腺素合成酶、细胞色素P450)的人非常感兴趣。所采用的方法是多学科的，将有助于形成高素质的人员。

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.