Global RNA fold and molecular recognition for a pfl riboswitch bound to ZMP, a master regulator of one-carbon metabolism Journal Article
| Authors: | Ren, A.; Rajashankar, K. R.; Patel, D. J. |
| Article Title: | Global RNA fold and molecular recognition for a pfl riboswitch bound to ZMP, a master regulator of one-carbon metabolism |
| Abstract: | Summary ZTP, the pyrophosphorylated analog of ZMP (5-amino-4-imidazole carboxamide ribose-5′-monophosphate), was identified as an alarmone that senses 10-formyl-tetrahydroflate deficiency in bacteria. Recently, a pfl riboswitch was identified that selectively binds ZMP and regulates genes associated with purine biosynthesis and one-carbon metabolism. We report on the structure of the ZMP-bound Thermosinus carboxydivorans pfl riboswitch sensing domain, thereby defining the pseudoknot-based tertiary RNA fold, the binding-pocket architecture, and principles underlying ligand recognition specificity. Molecular recognition involves shape complementarity, with the ZMP 5-amino and carboxamide groups paired with the Watson-Crick edge of an invariant uracil, and the imidazole ring sandwiched between guanines, while the sugar hydroxyls form intermolecular hydrogen bond contacts. The burial of the ZMP base and ribose moieties, together with unanticipated coordination of the carboxamide by Mg2+, contrasts with exposure of the 5′-phosphate to solvent. Our studies highlight the principles underlying RNA-based recognition of ZMP, a master regulator of one-carbon metabolism. © 2015 Elsevier Ltd. |
| Keywords: | nonhuman; binding affinity; genetic association; gene expression regulation; guanine; molecular recognition; amino acid; crystal structure; hydrogen bond; regulatory rna sequence; bacterium; rna binding; carbon; amide; riboswitch; sugar; magnesium; hydrogen; bacterial metabolism; hydroxyl group; uracil; bacterial rna; ribose; imidazole; rna folding; carbon metabolism; priority journal; article; purine synthesis; 5 amino 4 imidazolecarboxamide riboside phosphate; organisms by carbon source; thermosinus carboxydivorans |
| Journal Title: | Structure |
| Volume: | 23 |
| Issue: | 8 |
| ISSN: | 0969-2126 |
| Publisher: | Cell Press |
| Date Published: | 2015-08-04 |
| Start Page: | 1375 |
| End Page: | 1381 |
| Language: | English |
| DOI: | 10.1016/j.str.2015.05.016 |
| PROVIDER: | scopus |
| PUBMED: | 26118534 |
| PMCID: | PMC4685959 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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