DNA building blocks: keeping control of manufacture.
DNA building blocks: keeping control of manufacture.
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DOI：
10.3109/10409238.2011.630372
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发表时间：
2012-01
影响因子：
6.5
通讯作者：
Sjöberg BM
中科院分区：
文献类型：
--
作者：
Hofer A;Crona M;Logan DT;Sjöberg BM
核糖核苷酸还原酶 (RNR) 是从头生产 DNA 合成和修复所需的四种脱氧核糖核苷三磷酸 (dNTP) 结构单元的唯一来源。仔细平衡这些 dNTP 池至关重要，因为当 dNTP 水平不平衡或升高时，突变率会增加。 RNR 是这种稳态的主要参与者，凭借其四种不同的底物、四种不同的变构效应器和两个不同的效应器结合位点，它具有当今已知的最复杂的变构调节之一。在过去的几年中，在变构效应子和底物存在的情况下，已经确定了几种细菌、酵母和人类的 RNR 结构，揭示了有关变构调节机制的新信息。所有研究的 RNR 的一个共同主题是一个灵活的环，它介导从变构特异性位点（s 位点）到催化位点的调节作用，以区分四种底物。对于变构活性位点（a 位点）知之甚少，该位点通过结合 ATP（激活剂）或 dATP（抑制剂）充当酶整体活性的开关。这两种核苷酸诱导不同酶寡聚体的形成，酵母中 dATP 抑制的 α6β2 复合物的最新结构表明其亚基如何非生产性地相互作用。有趣的是，真核生物和大肠杆菌之间形成的寡聚体及其变构调节的细节有所不同。然而，这些差异在一种必需酶中具有共同的目的，其变构调节可能可以追溯到中心法则背后的分子机制进化的时代。
Ribonucleotide reductase (RNR) is the only source for de novo production of the four deoxyribonucleoside triphosphate (dNTP) building blocks needed for DNA synthesis and repair. It is crucial that these dNTP pools are carefully balanced, since mutation rates increase when dNTP levels are either unbalanced or elevated. RNR is the major player in this homeostasis, and with its four different substrates, four different allosteric effectors and two different effector binding sites, it has one of the most sophisticated allosteric regulations known today. In the past few years, the structures of RNRs from several bacteria, yeast and man have been determined in the presence of allosteric effectors and substrates, revealing new information about the mechanisms behind the allosteric regulation. A common theme for all studied RNRs is a flexible loop that mediates modulatory effects from the allosteric specificity site (s-site) to the catalytic site for discrimination between the four substrates. Much less is known about the allosteric activity site (a-site), which functions as an on-off switch for the enzyme's overall activity by binding ATP (activator) or dATP (inhibitor). The two nucleotides induce formation of different enzyme oligomers, and a recent structure of a dATP-inhibited α6β2 complex from yeast suggested how its subunits interacted non-productively. Interestingly, the oligomers formed and the details of their allosteric regulation differ between eukaryotes and Escherichia coli Nevertheless, these differences serve a common purpose in an essential enzyme whose allosteric regulation might date back to the era when the molecular mechanisms behind the central dogma evolved.
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影响因子：
4.8
作者：
Andersson, J;Westman, M;Sjöberg, BM
通讯作者：
Sjöberg, BM
影响因子：
30.8
作者：
Bourdon, Alice;Minai, Limor;Rotig, Agnes
通讯作者：
Rotig, Agnes
影响因子：
5.3
作者：
CARAS, IW;MARTIN, DW
通讯作者：
MARTIN, DW
影响因子：
5.6
作者：
BROWN, NC;REICHARD, P
通讯作者：
REICHARD, P
DOI：
10.1073/pnas.1013274108
发表时间：
2011-06-14
影响因子：
11.1
作者：
Aye, Yimon;Stubbe, JoAnne
通讯作者：
Stubbe, JoAnne