Saccharide-RNA recognition in an aminoglycoside antibiotic-RNA aptamer complex Journal Article
| Authors: | Jiang, L.; Suri, A. K.; Fiala, R.; Patel, D. J. |
| Article Title: | Saccharide-RNA recognition in an aminoglycoside antibiotic-RNA aptamer complex |
| Abstract: | Background: Aminoglycoside antibiotics are known to target ribosomal, retroviral and catalytic RNAs with high affinity and specificity. Recently, in vitro selection experiments have identified RNA aptamers that bind to aminoglycoside antibiotics with nanomolar affinity and stringent specificity, allowing discrimination between closely related family members. There has, to date, been limited structural information on the molecular basis of such saccharide-RNA recognition. Results: We describe a solution-structure determination of the tobramycin-RNA aptamer complex, obtained using NMR and molecular dynamics. The structure gives insight into the molecular features associated with saccharide-RNA recognition. Tobramycin adopts a defined alignment and binds to the RNA major groove centered about a stem-loop junction site. A portion of the bound tobramycin is encapsulated between the floor of the major groove and a looped-out cytosine residue that forms a flap over the binding site in the complex. Conclusions: The emergence of antibiotic-resistant pathogens and their impact on human health continues to be a major concern in the medical community. Rational modification of existing antibiotics aimed at improving their efficacy requires a molecular view of their receptor-binding sites. We have provided such a molecular view for a member of the aminoglycoside antibiotic family that targets RNA. |
| Keywords: | molecular genetics; metabolism; rna; antiinfective agent; antibiotic resistance; chemistry; anti-bacterial agents; molecular sequence data; nucleotide sequence; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; base sequence; binding site; computer simulation; models, molecular; binding sites; chemical structure; tobramycin; carbohydrate analysis; carbohydrate sequence; carbohydrates; carbohydrate; audiovisual equipment; drug resistance, microbial; oligoribonucleotide; oligoribonucleotides; humans; human; article; models, structural; aminoglycoside-rna recognition; rna u-turn motif; saccharide targeting the rna major groove |
| Journal Title: | Chemistry and Biology |
| Volume: | 4 |
| Issue: | 1 |
| ISSN: | 1074-5521 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1997-01-01 |
| Start Page: | 35 |
| End Page: | 50 |
| Language: | English |
| PUBMED: | 9070426 |
| PROVIDER: | scopus |
| DOI: | 10.1016/S1074-5521(97)90235-0 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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