کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1393650 | 983966 | 2014 | 12 صفحه PDF | دانلود رایگان |
• Though most THF riboswitches contain two binding sites, one is not vital for function
• The pABA moiety of THF greatly enhances regulatory activity, but not binding affinity
• Some well-established antifolates can regulate the riboswitch’s activity
• Adenine and derivatives exhibit “retro-binding” to the THF riboswitch
SummaryThe 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 were examined. Our data reveal that although 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.
Journal: - Volume 21, Issue 2, 20 February 2014, Pages 205–216