Mechanism for transcriptional action of cyclic AMP in Escherichia coli: entry into DNA to disrupt DNA secondary structure.
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.
D000242:Cyclic AMP / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D007211:Indoles / Q000378:metabolism; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D011485:Protein Binding; D011953:Receptors, Cyclic AMP / Q000502:physiology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*
D004269:DNA, Bacterial; D007211:Indoles; D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP