The alternative aerobic ribonucleotide reductase of Escherichia coli, NrdEF, is a manganese-dependent enzyme that enables cell replication during periods of iron starvation.

The alternative aerobic ribonucleotide reductase of Escherichia coli, NrdEF, is a manganese-dependent enzyme that enables cell replication during periods of iron starvation.
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DOI:
10.1111/j.1365-2958.2011.07593.x
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发表时间:
2011-04
影响因子:
3.6
通讯作者:
Imlay JA
Imlay JA
中科院分区:
生物学2区
文献类型:
--
作者:
Martin JE;Imlay JA

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大肠杆菌的基因组编码两种I类核糖核苷酸还原酶。第一种是NrdAB,它是一种被充分研究的铁依赖性酶,对有氧生长至关重要。第二个是NrdEF,在常规条件下不起作用,其作用也不清楚。最近的研究表明,NrdEF可以在体外激活锰以及铁。由于铁酶是过氧化氢的潜在靶点,并且由于nrdHIEF操纵子在H2O2应激期间被诱导,因此我们假设H2O2可能使NrdAB受损,并且NrdEF可能被诱导以补偿。这个想法是用E.大肠杆菌的突变体,长期强调过氧化氢。与预期相反,NrdAB仍然活跃。它对H_2O_2的抗性依赖于YfaE,YfaE有助于激活NrdB。在H2O2胁迫期间NrdEF的诱导是由铁依赖性阻遏物Fur的失活介导的。这种调节安排意味着NrdEF在铁饥饿期间具有生理作用。事实上,NrdEF支持铁耗尽细胞中的细胞复制。当NrdF在富含铁的细胞中表达时,铁与NrdF结合,但NrdEF仅在缺铁和富锰的细胞中起作用。因此,当铁不能激活管家NrdAB酶时,NrdEF支持DNA复制。
The genome of Escherichia coli encodes two class I ribonucleotide reductases. The first, NrdAB, is a well-studied iron-dependent enzyme that is essential for aerobic growth. The second, NrdEF, is not functional under routine conditions, and its role is obscure. Recent studies demonstrated that NrdEF can be activated in vitro by manganese as well as iron. Since iron enzymes are potential targets for hydrogen peroxide, and since the nrdHIEF operon is induced during H2O2 stress, we hypothesized that H2O2 might inactivate NrdAB and that NrdEF might be induced to compensate. This idea was tested using E. coli mutants that are chronically stressed by H2O2. Contrary to expectation, NrdAB remained active. Its resistance to H2O2 depended upon YfaE, which helps to activate NrdB. The induction of NrdEF during H2O2 stress was mediated by the inactivation of Fur, an iron-dependent repressor. This regulatory arrangement implied that NrdEF has a physiological role during periods of iron starvation. Indeed, NrdEF supported cell replication in iron-depleted cells. Iron bound to NrdF when it was expressed in iron-rich cells, but NrdEF was functional only in cells that were both iron-depleted and manganese-rich. Thus NrdEF supports DNA replication when iron is unavailable to activate the housekeeping NrdAB enzyme.
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