1fyp
From Proteopedia
(New page: 200px<br /><applet load="1fyp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fyp" /> '''EUKARYOTIC DECODING REGION A-SITE RNA-PAROMO...) |
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'''EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX'''<br /> | '''EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Aminoglycoside antibiotics, including paromomycin, neomycin and | + | 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== | ==About this Structure== | ||
| - | 1FYP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with PAR as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1FYP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=PAR:'>PAR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYP OCA]. |
==Reference== | ==Reference== | ||
Structural origins of aminoglycoside specificity for prokaryotic ribosomes., Lynch SR, Puglisi JD, J Mol Biol. 2001 Mar 9;306(5):1037-58. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11237617 11237617] | Structural origins of aminoglycoside specificity for prokaryotic ribosomes., Lynch SR, Puglisi JD, J Mol Biol. 2001 Mar 9;306(5):1037-58. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11237617 11237617] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Lynch, S | + | [[Category: Lynch, S R.]] |
| - | [[Category: Puglisi, J | + | [[Category: Puglisi, J D.]] |
[[Category: PAR]] | [[Category: PAR]] | ||
[[Category: aminoglycoside]] | [[Category: aminoglycoside]] | ||
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[[Category: stem-internal loop-stem-tetraloop]] | [[Category: stem-internal loop-stem-tetraloop]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:44:03 2008'' |
Revision as of 10:44, 21 February 2008
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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 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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