Gardner P R, Gardner A M, Martin L A, Salzman A L
Division of Critical Care Medicine, Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10378-83. doi: 10.1073/pnas.95.18.10378.
Nitric oxide (NO*) is a toxin, and various life forms appear to have evolved strategies for its detoxification. NO*-resistant mutants of Escherichia coli were isolated that rapidly consumed NO*. An NO*-converting activity was reconstituted in extracts that required NADPH, FAD, and O2, was cyanide-sensitive, and produced NO3-. This nitric oxide dioxygenase (NOD) contained 19 of 20 N-terminal amino acids identical to those of the E. coli flavohemoglobin. Furthermore, NOD activity was produced by the flavohemoglobin gene and was inducible by NO*. Flavohemoglobin/NOD-deficient mutants were also sensitive to growth inhibition by gaseous NO*. The results identify a function for the evolutionarily conserved flavohemoglobins and, moreover, suggest that NO* detoxification may be a more ancient function for the widely distributed hemoglobins, and associated methemoglobin reductases, than dioxygen transport and storage.
一氧化氮（NO*）是一种毒素，各种生命形式似乎已经进化出对其进行解毒的策略。分离出了对NO具有抗性的大肠杆菌突变体，这些突变体能够快速消耗NO。在需要NADPH、FAD和O2的提取物中重建了一种NO转化活性，该活性对氰化物敏感，并产生NO3-。这种一氧化氮双加氧酶（NOD）的20个N端氨基酸中有19个与大肠杆菌黄素血红蛋白的相同。此外，黄素血红蛋白基因可产生NOD活性，且该活性可被NO诱导。缺乏黄素血红蛋白/NOD的突变体对气态NO的生长抑制也很敏感。这些结果确定了进化上保守的黄素血红蛋白的一种功能，此外，还表明与双加氧运输和储存相比，NO解毒可能是广泛分布的血红蛋白及相关高铁血红蛋白还原酶更古老的功能。
