Max-Planck-Institut für Bioanorganische Chemie, Mülheim an der Ruhr, Germany.
IUBMB Life. 2011 May;63(5):304-12. doi: 10.1002/iub.451. Epub 2011 Apr 13.
Nitrophorins (NPs) comprise a unique class of heme proteins used by the blood-sucking insect Rhodnius prolixus to deliver the signaling gas molecule NO into the blood vessel of a host during feeding. Upon NO release, histamine can be scavenged by coordination to the heme iron. Although the protein is of similar size as the mammalian globin monomers and shares the same cofactor and proximal histidine coordination, nitrophorin structure, in contrast, is almost entirely composed of a β-barrel. Comparison of the NO and histamine association constants with the concentrations of both compounds invivo raises concerns about the very simple ligand release model in case of at least some of the NPs. Therefore, novel functionalities of the NPs were sought. As a result, catalysis of the nitrite disproportionation reaction was found, which leads to the formation of NO with nitrite as the sole substrate. This is the first example of a ferriheme protein that can perform this reaction. Furthermore, although NPs stabilize the ferriheme state, a peroxidase reactivity of the cofactor involving the higher oxidation state iron (Compound I/II) was studied with the potential to catalyze the oxidation of histamine and norepinephrine. In contrast to many other heme proteins including the globins, the ferroheme state was found to be extremely sensitive to O(2) , which is a consequence of the much lower reduction potential of the NPs, so that the 1-electron reduction of O(2) to O (•-)(2) becomes a thermodynamically favored process. Altogether, the detailed study of the NPs gives insight into the structure-function relationships required for the targeted delivery of diatomic gas molecules in biology. Moreover, the comparison of the structure-function relationships of the NPs (NO transporters) with those of the globins (O(2) transporters) will help to elucidate the architectural requirement for the respective tasks.
硝普蛋白（NPs）是一类独特的血红素蛋白，吸血昆虫丽蝇（Rhodnius prolixus）在吸血时将信号气体分子一氧化氮（NO）输送到宿主的血管中。在 NO 释放后，组胺可以通过与血红素铁配位而被清除。尽管该蛋白的大小与哺乳动物球蛋白单体相似，并共享相同的辅因子和近端组氨酸配位，但硝普蛋白的结构几乎完全由β-桶组成。比较 NO 和组胺的结合常数与两者在体内的浓度，引起了人们对至少一些 NPs 中非常简单的配体释放模型的关注。因此，人们寻求 NPs 的新功能。结果发现，硝普蛋白能够催化亚硝酸盐歧化反应，这导致以亚硝酸盐为唯一底物形成 NO。这是首例能够进行该反应的亚铁血红素蛋白。此外，尽管 NPs 稳定了亚铁血红素状态，但研究了辅因子的过氧化物酶反应性，涉及更高氧化态铁（化合物 I/II），具有催化组胺和去甲肾上腺素氧化的潜力。与包括球蛋白在内的许多其他血红素蛋白不同，亚铁血红素状态对 O(2)极其敏感，这是由于 NPs 的还原电位低得多，因此 O(2)的 1 电子还原为 O (•-)(2)成为一个热力学有利的过程。总之，对硝普蛋白的详细研究深入了解了生物学中双原子气体分子靶向输送所需的结构-功能关系。此外，将 NPs（NO 转运蛋白）的结构-功能关系与球蛋白（O(2)转运蛋白）的结构-功能关系进行比较，将有助于阐明各自任务的结构要求。
