Apramycin recognition by the human ribosomal decoding site Journal Article
| Authors: | Hermann, T.; Terechko, V.; Skripkin, E.; Patel, D. J. |
| Article Title: | Apramycin recognition by the human ribosomal decoding site |
| Abstract: | Aminoglycoside antibiotics bind specifically to the bacterial ribosomal decoding-site RNA and thereby interfere with fidelity but not efficiency of translation. Apramycin stands out among aminoglycosides for its mechanism of action which is based on blocking translocation and its ability to bind also to the eukaryotic decoding site despite differences in key residues required for apramycin recognition by the bacterial target. To elucidate molecular recognition of the eukaryotic decoding site by apramycin we have determined the crystal structure of an oligoribonucleotide containing the human sequence free and in complex with the antibiotic at 1.5 Å resolution. The drug binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-canonical C{filled circle}A and G{filled circle}A base pairs and a bulged-out adenine. The binding mode of apramycin at the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target, suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; sequence analysis; nonhuman; structure-activity relationship; bacteria (microorganisms); rna; guanine; eukaryota; rna translation; base pairing; crystal structure; models, molecular; binding sites; molecular structure; nucleic acid conformation; ribosome rna; rna, ribosomal; drug binding site; drug binding; x-ray crystallography; adenine; neomycin; ribosome; cytosine; rna conformation; aminoglycoside antibiotics; ribosomal decoding site; apramycin; nebramycin |
| Journal Title: | Blood Cells, Molecules, and Diseases |
| Volume: | 38 |
| Issue: | 3 |
| ISSN: | 1079-9796 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2007-05-01 |
| Start Page: | 193 |
| End Page: | 198 |
| Language: | English |
| DOI: | 10.1016/j.bcmd.2006.11.006 |
| PUBMED: | 17258916 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: BCMDF" - "Source: Scopus" |
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