A disconnect between high-affinity binding and efficient regulation by antifolates and purines in the tetrahydrofolate riboswitch.
A disconnect between high-affinity binding and efficient regulation by antifolates and purines in the tetrahydrofolate riboswitch.
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DOI：
10.1016/j.chembiol.2013.11.012
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发表时间：
2014-02-20
影响因子：
--
通讯作者：
Batey RT
中科院分区：
文献类型：
--
作者：
Trausch JJ;Batey RT
四氢叶酸（THF）核糖开关通过协同结合两个THF分子来调控许多厚壁菌门细菌中的叶酸转运和代谢。为了进一步了解这种核糖开关对THF的特异性，研究人员检测了一系列THF类似物和抗叶酸剂的结合及调控活性。我们的数据显示，尽管结合主要由RNA与蝶呤部分的相互作用所主导，但对氨基苯甲酸（pABA）部分在转录调控中起着重要作用。此外，我们发现腺嘌呤和其他几种类似物通过一种替代结合机制以高亲和力结合。尽管腺嘌呤与THF具有相似的亲和力，但它是一种较差的转录衰减调控因子。这些结果表明，单独的结合并不能决定一种化合物在调控核糖开关活性方面的有效性——这是当前开发针对这些RNA的抗菌药物的努力中的一个复杂情况。
The tetrahydrofolate (THF) riboswitch regulates folate transport and metabolism in a number of Firmicutes by cooperatively binding two molecules of THF. To further understand this riboswitch’s specificity for THF, binding and regulatory activity of a series of THF analogs and antifolates was examined. Our data reveal that while binding is dominated by the RNA’s interactions with the pterin moiety, the para-aminobenzoic acid (pABA) moiety plays a significant role in transcriptional regulation. Further, we find that adenine and several other analogs bind with high affinity by an alternative binding mechanism. Despite a similar affinity to THF, adenine is a poor regulator of transcriptional attenuation. These results demonstrate that binding alone does not determine a compound’s effectiveness in regulating the activity of the riboswitch—a complication in current efforts to develop antimicrobials that target these RNAs.
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影响因子：
18.3
作者：
Deigan, Katherine E.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.
DOI：
10.1073/pnas.1111701108
发表时间：
2011-09-06
影响因子：
11.1
作者：
Huang, Lili;Ishibe-Murakami, Satoko;Serganov, Alexander
通讯作者：
Serganov, Alexander
影响因子：
15
作者：
Gilbert, Sunny D.;Mediatore, Sarah J.;Batey, Robert T.
通讯作者：
Batey, Robert T.
影响因子：
--
作者：
Ames TD;Rodionov DA;Weinberg Z;Breaker RR
通讯作者：
Breaker RR
影响因子：
8.4
作者：
Cressina, Elena;Chen, Liuhong;Smith, Alison G.
通讯作者：
Smith, Alison G.