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New page: left|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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[[Image:1fyp.gif|left|200px]]<br /><applet load="1fyp" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1fyp" />
'''EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX'''<br />


==Overview==
==EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX==
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.
<StructureSection load='1fyp' size='340' side='right'caption='[[1fyp]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fyp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FYP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PAR:PAROMOMYCIN'>PAR</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1fyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fyp OCA], [https://pdbe.org/1fyp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fyp RCSB], [https://www.ebi.ac.uk/pdbsum/1fyp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fyp ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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==
Structural origins of aminoglycoside specificity for prokaryotic ribosomes.,Lynch SR, Puglisi JD J Mol Biol. 2001 Mar 9;306(5):1037-58. PMID:11237617<ref>PMID:11237617</ref>
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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FYP OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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]
</div>
[[Category: Protein complex]]
<div class="pdbe-citations 1fyp" style="background-color:#fffaf0;"></div>
[[Category: Lynch, S.R.]]
== References ==
[[Category: Puglisi, J.D.]]
<references/>
[[Category: PAR]]
__TOC__
[[Category: aminoglycoside]]
</StructureSection>
[[Category: g-a base pair]]
[[Category: Large Structures]]
[[Category: rna-drug]]
[[Category: Lynch SR]]
[[Category: rna-paromomycin complex]]
[[Category: Puglisi JD]]
[[Category: stem-internal loop-stem-tetraloop]]
 
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EUKARYOTIC DECODING REGION A-SITE RNA-PAROMOMYCIN COMPLEX

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