Hemoglobin: a nitric-oxide dioxygenase.
Hemoglobin: a nitric-oxide dioxygenase.
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DOI：
10.6064/2012/683729
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发表时间：
2012
期刊：
影响因子：
3.2
通讯作者：
Gardner PR
中科院分区：
文献类型：
--
作者：
Gardner PR
血红蛋白超家族的成员有效地催化一氧化氮双加氧，并且当与天然电子供体配对时，作为NO双加氧酶（NOD）起作用。事实上，NOD功能已经成为一个更常见和古老的功能，而不是众所周知的O2运输-储存功能。具有NOD功能的新型血红蛋白在各种生命形式中不断被发现。独特的血红蛋白结构的演变，部分原因是不同的电子供体的催化作用。NOD催化的代表性的单域血红蛋白和多域黄素血红蛋白的机制发生通过多步机制，涉及O2迁移到血红素口袋，O2结合还原，NO迁移，自由基-自由基耦合，O-原子重排，硝酸盐释放，和血红素铁再还原。揭示多种NODs在生物体中不同表达的生理功能以及NO作为毒物和信号分子的复杂性仍然是NO领域的巨大挑战。NOD敲除生物体和表达重组NOD的细胞有助于促进我们对NO在微生物感染、植物衰老、癌症、线粒体功能、铁代谢和组织O2稳态中的作用的理解。NOD抑制剂正作为抗生素和抗肿瘤剂用于治疗应用。转基因表达NOD的植物、鱼、藻类和微生物正在被开发用于农业、水产养殖和工业。
Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs). Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry.