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Structure of the THF riboswitch bound to 2,6-diaminopurineStructure of the THF riboswitch bound to 2,6-diaminopurine
Structural highlights
Publication Abstract from PubMedThe 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. A Disconnect between High-Affinity Binding and Efficient Regulation by Antifolates and Purines in the Tetrahydrofolate Riboswitch.,Trausch JJ, Batey RT Chem Biol. 2014 Feb 20;21(2):205-16. doi: 10.1016/j.chembiol.2013.11.012. Epub, 2014 Jan 2. PMID:24388757[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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OCA- Batey, R T
- Trausch, J J
- 6-diaminopurine
- Aptamer
- Bacillus subtili
- Bacterial
- Bacterial protein
- Base sequence
- Binding site
- Calorimetry
- Folic acid
- Gene expression regulation
- Genetic
- Guanine
- Leucovorin
- Ligand
- Magnesium
- Molecular sequence data
- Mrna
- Ncrna
- Nucleic acid conformation
- Nucleotide
- Point mutation
- Protein binding
- Protein structure
- Pseudoknot
- Regulation
- Riboswitch
- Rna
- S-adenosylmethionine
- Secondary
- Streptococcus mutan
- Terminator region
- Tetrahydrofolate
- Thermodynamic
- Three-way junction
- Transcription