A disconnect between high-affinity binding and efficient regulation by antifolates and purines in the tetrahydrofolate riboswitch.

ABSTRACT: 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 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 effective

SUBMITTER: Trausch JJ 

PROVIDER: S-EPMC3935398 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature