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1fyp

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1fyp

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EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX

Overview

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.

About this Structure

1FYP is a Protein complex structure of sequences from [1] with PAR as ligand. Full crystallographic information is available from OCA.

Reference

Structural origins of aminoglycoside specificity for prokaryotic ribosomes., Lynch SR, Puglisi JD, J Mol Biol. 2001 Mar 9;306(5):1037-58. PMID:11237617

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