Khatua Suman, Majumdar Amit
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
J Inorg Biochem. 2015 Jan;142:145-53. doi: 10.1016/j.jinorgbio.2014.09.018. Epub 2014 Oct 13.
Inducible NO synthase in mammals helps to produce up to micromolar concentration of nitric oxide (NO) which acts as a key immune defense agent to kill invading pathogens. In order to counter the toxic effects of NO, the pathogens have expressed flavodiiron nitric oxide reductases (FNORs). The FNORs reduce the toxic NO into much less toxic N2O and thus help the pathogens to survive under nitrosative stress. As a consequence, these pathogens proliferate in the human body and cause harmful infections. An appreciable amount of research work has been performed to discover the true mechanism of the FNORs. Different mechanisms involving both mononitrosyl and dinitrosyl diiron complexes as key intermediates are proposed. Evidences for the involvement of new intermediates and more and more experimental evidences for existing ones in the proposed catalytic cycle of FNORs are coming up. These interesting biochemical events have recently boosted the biomimetic chemistry of the FNOR activity as well. This article discusses the importance and the currently understood mechanistic aspects of FNORs. Structural and functional models for the active site of FNORs are discussed along with their success and limitations. Possible future prospects of the modeling chemistry are also suggested.
哺乳动物体内的诱导型一氧化氮合酶有助于产生高达微摩尔浓度的一氧化氮（NO），它作为一种关键的免疫防御因子，可杀死入侵的病原体。为了对抗NO的毒性作用，病原体表达了黄素二铁一氧化氮还原酶（FNORs）。FNORs将毒性较强的NO还原为毒性小得多的N2O，从而帮助病原体在亚硝化应激下存活。因此，这些病原体在人体内增殖并引发有害感染。人们已经开展了大量研究工作来揭示FNORs的真实作用机制。有人提出了不同的机制，其中涉及单亚硝酰基和二亚硝酰基二铁配合物作为关键中间体。在FNORs的催化循环中，越来越多关于新中间体参与以及现有中间体的实验证据不断涌现。这些有趣的生化事件最近也推动了FNOR活性的仿生化学研究。本文讨论了FNORs的重要性以及目前所了解的作用机制。文中还讨论了FNORs活性位点的结构和功能模型，以及它们的成功之处和局限性。此外，还提出了建模化学可能的未来前景。
