Mechanism for transcriptional action of cyclic AMP in Escherichia coli: entry into DNA to disrupt DNA secondary structure.
Mechanism for transcriptional action of cyclic AMP in Escherichia coli: entry into DNA to disrupt DNA secondary structure.
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环AMP在大肠杆菌中的转录作用机制：进入DNA破坏DNA二级结构。
DOI：
10.1073/pnas.78.7.4011
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发表时间：
1981
影响因子：
11.1
通讯作者：
Wong,JR
中科院分区：
文献类型：
--
作者：
Ebright,RH;Wong,JR
与纯化的细菌受体的结合分析表明，cAMP有两个结构域。第一个是环状磷酸和呋喃糖，构成一个结合域。这一区域与受体紧密结合。CAMP的其余部分不受束缚；cAMP的腺嘌呤部分暴露出来。与结合不同，cAMP的活性需要腺嘌呤部分。要发挥活性，cAMP必须在结构域II中具有碱基腺嘌呤--具体地说，是它的沃森-克里克原子N-1和N-6。对吲哚乙酸的分析表明，结合区域和活性区域之间存在类似的区别。吲哚乙酸是一种能够取代L-阿拉伯糖操纵子上cAMP的化合物。为了具有活性，吲哚必须具有与cAMP N-1和N-6电子相当的取代(羧基或酰胺)。在此基础上，我们提出了cAMP(或吲哚乙酸)在大肠杆菌中作用的详细机制。我们认为暴露在cAMP中的腺嘌呤进入DNA。腺嘌呤的N-1和N-6与DNA中的胸腺嘧啶形成氢键。这种相互作用会破坏DNA的稳定。它能增强转录。显著的相似性表明，真核生物中的类固醇激素具有相同的机制。
Binding analysis with purified bacterial receptor distinguishes two structural domains in cyclic AMP (cAMP). The first, the cyclic phosphate and furanose, constitutes a binding domain. This region is bound tightly to the receptor. The rest of cAMP is not bound; the adenine moiety of cAMP is exposed. Unlike binding, activity of cAMP requires the adenine moiety. To be active, cAMP must have in domain II the base adenine--specifically, its Watson--Crick atoms N-1 and N-6. Analysis of indoleacetic acid, a compound able to replace cAMP at the L-arabinose operon, indicates a similar distinction between binding and active domains. To be active, the indole must have substitution (carboxyl or amide) electronically comparable to the cAMP N-1 and N-6. On this basis, we propose a detailed mechanism for action of cAMP (or indoleacetic acid) in Escherichia coli. We propose that the exposed adenine of cAMP enters into the DNA. The adenine's N-1 and N-6 form hydrogen bonds to a thymine in DNA. This interaction destabilizes the DNA. It enhances transcription. Marked similarities indicate an identical mechanism for the steroid hormones in eukaryotes.