Drapier J C, Bouton C
U 365 INSERM, Section de Recherche, Institut Curie, Paris, France.
Bioessays. 1996 Jul;18(7):549-56. doi: 10.1002/bies.950180706.
In many cells, a nitric oxide (NO) synthase inducible by immunological stimuli produces a sustained flow of NO that lasts a long time. NO is a short-lived molecule but it is a diffusible ligand believed to be capable of reaching distal target sites. Further, several lines of evidence indicate that cysteine-rich motifs of metal-binding proteins, as well as redox-sensitive metal clusters of metalloproteins, are natural sensors of bioradicals like NO. In metalloregulatory proteins, metals are often conveniently located at binding sites and bound to cysteine residues. Accordingly, disruption of the metal-thiolate polymetallic clusters should trigger significant remodelling of the protein structure involved in regulation. We can therefore postulate that the nitrosation reaction occurring at metal centres or cysteine-rich motifs will preclude correct binding to regulatory sites. Several examples are given of metalloregulatory proteins whose metal is bound to thiols and may then become sensitive to NO. Recent observations indicate that in response to NO synthesis, iron regulatory protein, a eukaryotic bifunctional [Fe-S] protein, switches from acting as aconitase to being an RNA-binding regulator, and we suggest that the interplay between NO or a NO-derived molecule and metal clusters at critical allosteric sites may be a crucial component of the cellular response to environmental stress.
在许多细胞中，一种可被免疫刺激诱导的一氧化氮（NO）合酶会产生持续时间很长的NO流。NO是一种寿命短暂的分子，但它是一种可扩散的配体，据信能够到达远端靶位点。此外，多条证据表明，金属结合蛋白富含半胱氨酸的基序以及金属蛋白的氧化还原敏感金属簇，是诸如NO等生物自由基的天然传感器。在金属调节蛋白中，金属通常方便地位于结合位点并与半胱氨酸残基结合。因此，金属硫醇盐多金属簇的破坏应该会引发参与调节的蛋白质结构的显著重塑。我们因此可以推测，在金属中心或富含半胱氨酸的基序处发生的亚硝化反应将阻止与调节位点的正确结合。文中给出了几个金属调节蛋白的例子，其金属与硫醇结合，然后可能对NO变得敏感。最近的观察结果表明，响应于NO合成，铁调节蛋白，一种真核双功能[Fe-S]蛋白，从作为乌头酸酶转变为RNA结合调节因子，并且我们认为在关键变构位点处NO或NO衍生分子与金属簇之间的相互作用可能是细胞对环境应激反应的关键组成部分。
