Signal perception by FNR: the role of the iron-sulfur cluster
Signal perception by FNR: the role of the iron-sulfur cluster
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DOI：
10.1042/bst0361144
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发表时间：
2008-12-01
影响因子：
3.9
通讯作者：
Le Brun, Nick E.
中科院分区：
文献类型：
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作者：
Crack, Jason C.;Jervis, Adrian J.;Le Brun, Nick E.
细菌的代谢灵活性是它们在各种环境中生存和繁衍的能力的关键。从一种代谢途径到另一种代谢途径的最佳切换是这种灵活性的关键要求。呼吸就是一个很好的例子：许多细菌利用 O-2 作为末端电子受体，但当 O-2 受到限制时，它们可以切换到一系列其他受体，例如硝酸盐。感知环境中的 O-2 水平是从有氧呼吸转换为无氧呼吸的关键步骤。在大肠杆菌中，富马酸和硝酸盐还原转录调节因子 (FNR) 控制着这一开关。在O-2限制条件下，FNR结合[4Fe-4S](2+)簇，产生转录活性二聚体形式。暴露于 O-2 会导致簇转化为 [2Fe-2S](2+) 形式，从而导致蛋白质解离成无活性单体。簇转化的机制以及反应产物的性质目前引起了人们极大的兴趣，并且现在已经出现了对该过程的近乎完整的描述。 [4Fe-4S](2+)到[2Fe-2S](2+)簇的转化通过两步机制进行。在步骤1中，簇发生单电子氧化，导致Fe2+离子的释放，形成中间[3Fe-4S](1+)簇，同时产生超氧阴离子。在步骤2中，中间体[3Fe-4S](1+)簇自发重排形成[2Fe-2S](2+)簇，在此过程中释放出两个硫离子和一个Fe3+离子。簇的单电子激活，与超氧化物歧化酶和过氧化氢酶将超氧阴离子催化再循环回氧相结合，提供了一种增强[4Fe-4S](2+) FNR对其信号分子的敏感性的新方法。
The metabolic flexibility of bacteria is key to their ability to survive and thrive in a wide range of environments. Optimal switching from one metabolic pathway to another is a key requirement for this flexibility. Respiration is a good example: many bacteria utilize O-2 as the terminal electron acceptor, but can switch to a range of other acceptors, such as nitrate, when O-2 becomes limiting. Sensing environmental levels of O-2 is the key step in switching from aerobic to anaerobic respiration. in Escherichia coli, the fumarate and nitrate reduction transcriptional regulator (FNR) controls this switch. Under O-2-limiting conditions, FNR binds a [4Fe-4S](2+) cluster, generating a transcriptionally active dimeric form. Exposure to O-2 results in conversion of the cluster into a [2Fe-2S](2+) form, leading to dissociation of the protein into inactive monomers. The mechanism of cluster conversion, together with the nature of the reaction products, is of considerable current interest, and a near-complete description of the process has now emerged. The [4Fe-4S](2+) into [2Fe-2S](2+) cluster conversion proceeds via a two-step mechanism. in step 1, a one-electron oxidation of the cluster takes place, resulting in the release of a Fe2+ ion, the formation of an intermediate [3Fe-4S](1+) cluster, together with the generation of a superoxide anion. In step 2, the intermediate [3Fe-4S](1+) cluster rearranges spontaneously to form the [2Fe-2S](2+) cluster, releasing two sulfide ions and an Fe3+ ion in the process. The one-electron activation of the cluster, coupled to catalytic recycling of the superoxide anion back to oxygen via superoxide dismutase and catalase, provides a novel means of amplifying the sensitivity of [4Fe-4S](2+) FNR to its signal molecule.