'''EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX'''
===EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX===
==Overview==
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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.
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{{ABSTRACT_PUBMED_11237617}}
==About this Structure==
==About this Structure==
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYP OCA].
Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYP OCA].
==Reference==
==Reference==
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[[Category: Rna-paromomycin complex]]
[[Category: Rna-paromomycin complex]]
[[Category: Stem-internal loop-stem-tetraloop]]
[[Category: Stem-internal loop-stem-tetraloop]]
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Revision as of 01:08, 1 July 2008
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