1FYP
EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX
Summary for 1FYP
| Entry DOI | 10.2210/pdb1fyp/pdb |
| Related | 1A3M 1FYO 1PBR |
| Descriptor | FRAGMENT OF 18S RIBOSOMAL RNA, PAROMOMYCIN (2 entities in total) |
| Functional Keywords | rna-paromomycin complex, aminoglycoside, stem-internal loop-stem-tetraloop, rna-drug, g-a base pair, rna |
| Total number of polymer chains | 1 |
| Total formula weight | 9287.81 |
| Authors | Lynch, S.R.,Puglisi, J.D. (deposition date: 2000-10-02, release date: 2001-03-14, Last modification date: 2024-05-22) |
| Primary citation | Lynch, S.R.,Puglisi, J.D. Structural origins of aminoglycoside specificity for prokaryotic ribosomes. J.Mol.Biol., 306:1037-1058, 2001 Cited by PubMed Abstract: Aminoglycoside antibiotics, including paromomycin, neomycin and gentamicin, target a region of highly conserved nucleotides in the decoding region aminoacyl-tRNA site (A site) of 16 S rRNA on the 30 S subunit. Change of a single nucleotide, A1408 to G, reduces the affinity of many aminoglycosides for the ribosome; G1408 distinguishes between prokaryotic and eukaryotic ribosomes. The structures of a prokaryotic decoding region A-site oligonucleotide free in solution and bound to the aminoglycosides paromomycin and gentamicin C1a were determined previously. Here, the structure of a eukaryotic decoding region A-site oligonucleotide bound to paromomycin has been determined using NMR spectroscopy and compared to the prokaryotic A-site-paromomycin structure. A conformational change in three adenosine residues of an internal loop, critical for high-affinity antibiotic binding, was observed in the prokaryotic RNA-paromomycin complex in comparison to its free form. This conformational change is not observed in the eukaryotic RNA-paromomycin complex, disrupting the binding pocket for ring I of the antibiotic. The lack of the conformational change supports footprinting and titration calorimetry data that demonstrate approximately 25-50-fold weaker binding of paromomycin to the eukaryotic decoding-site oligonucleotide. Neomycin, which is much less active against Escherichia coli ribosomes with an A1408G mutation, binds non-specifically to the oligonucleotide. These results suggest that eukaryotic ribosomal RNA has a shallow binding pocket for aminoglycosides, which accommodates only certain antibiotics. PubMed: 11237617DOI: 10.1006/jmbi.2000.4420 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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