2o3y: Difference between revisions

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New page: left|200px<br /><applet load="2o3y" size="350" color="white" frame="true" align="right" spinBox="true" caption="2o3y, resolution 2.700Å" /> '''Crystal Structure o...
 
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[[Image:2o3y.gif|left|200px]]<br /><applet load="2o3y" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2o3y, resolution 2.700&Aring;" />
'''Crystal Structure of the Homo sapiens Cytoplasmic Ribosomal Decoding Site in Presence of Paromamine Derivative NB30'''<br />


==Overview==
==Crystal Structure of the Homo sapiens Cytoplasmic Ribosomal Decoding Site in Presence of Paromamine Derivative NB30==
The lack of absolute prokaryotic selectivity of natural antibiotics is, widespread and is a significant clinical problem. The use of this, disadvantage of aminoglycoside antibiotics for the possible treatment of, human genetic diseases is extremely challenging. Here, we have used a, combination of biochemical and structural analysis to compare and contrast, the molecular mechanisms of action and the structure-activity, relationships of a new synthetic aminoglycoside, NB33, and a structurally, similar natural aminoglycoside apramycin. The data presented herein, demonstrate the general molecular principles that determine the decreased, selectivity of apramycin for the prokaryotic decoding site, and the, increased selectivity of NB33 for the eukaryotic decoding site. These, results are therefore extremely beneficial for further research on both, the design of new aminoglycoside-based antibiotics with diminished, deleterious effects on humans, as well as the design of new, aminoglycoside-based structures that selectively target the eukaryotic, ribosome.
<StructureSection load='2o3y' size='340' side='right'caption='[[2o3y]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2o3y]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O3Y FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SPM:SPERMINE'>SPM</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=2o3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o3y OCA], [https://pdbe.org/2o3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o3y RCSB], [https://www.ebi.ac.uk/pdbsum/2o3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o3y ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The lack of absolute prokaryotic selectivity of natural antibiotics is widespread and is a significant clinical problem. The use of this disadvantage of aminoglycoside antibiotics for the possible treatment of human genetic diseases is extremely challenging. Here, we have used a combination of biochemical and structural analysis to compare and contrast the molecular mechanisms of action and the structure-activity relationships of a new synthetic aminoglycoside, NB33, and a structurally similar natural aminoglycoside apramycin. The data presented herein demonstrate the general molecular principles that determine the decreased selectivity of apramycin for the prokaryotic decoding site, and the increased selectivity of NB33 for the eukaryotic decoding site. These results are therefore extremely beneficial for further research on both the design of new aminoglycoside-based antibiotics with diminished deleterious effects on humans, as well as the design of new aminoglycoside-based structures that selectively target the eukaryotic ribosome.


==About this Structure==
Differential selectivity of natural and synthetic aminoglycosides towards the eukaryotic and prokaryotic decoding A sites.,Kondo J, Hainrichson M, Nudelman I, Shallom-Shezifi D, Barbieri CM, Pilch DS, Westhof E, Baasov T Chembiochem. 2007 Sep 24;8(14):1700-9. PMID:17705310<ref>PMID:17705310</ref>
2O3Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=SPM:'>SPM</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O3Y OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Differential Selectivity of Natural and Synthetic Aminoglycosides towards the Eukaryotic and Prokaryotic Decoding A Sites., Kondo J, Hainrichson M, Nudelman I, Shallom-Shezifi D, Barbieri CM, Pilch DS, Westhof E, Baasov T, Chembiochem. 2007 Sep 24;8(14):1700-1709. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17705310 17705310]
</div>
[[Category: Single protein]]
<div class="pdbe-citations 2o3y" style="background-color:#fffaf0;"></div>
[[Category: Baasov, T.]]
== References ==
[[Category: Hainrichson, M.]]
<references/>
[[Category: Kondo, J.]]
__TOC__
[[Category: Nudelman, I.]]
</StructureSection>
[[Category: Shallom-Shezifi, D.]]
[[Category: Large Structures]]
[[Category: Westhof, E.]]
[[Category: Baasov T]]
[[Category: SPM]]
[[Category: Hainrichson M]]
[[Category: aminoglycoside]]
[[Category: Kondo J]]
[[Category: antibiotics]]
[[Category: Nudelman I]]
[[Category: cytoplasmic]]
[[Category: Shallom-Shezifi D]]
[[Category: decoding site]]
[[Category: Westhof E]]
[[Category: eukaryote]]
[[Category: homo sapiens]]
[[Category: ribosome]]
[[Category: rna]]
[[Category: stop codon readthrough]]
[[Category: translation inhibition]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:21:45 2008''

Latest revision as of 13:30, 30 August 2023

Crystal Structure of the Homo sapiens Cytoplasmic Ribosomal Decoding Site in Presence of Paromamine Derivative NB30Crystal Structure of the Homo sapiens Cytoplasmic Ribosomal Decoding Site in Presence of Paromamine Derivative NB30

Structural highlights

2o3y is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.7Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The lack of absolute prokaryotic selectivity of natural antibiotics is widespread and is a significant clinical problem. The use of this disadvantage of aminoglycoside antibiotics for the possible treatment of human genetic diseases is extremely challenging. Here, we have used a combination of biochemical and structural analysis to compare and contrast the molecular mechanisms of action and the structure-activity relationships of a new synthetic aminoglycoside, NB33, and a structurally similar natural aminoglycoside apramycin. The data presented herein demonstrate the general molecular principles that determine the decreased selectivity of apramycin for the prokaryotic decoding site, and the increased selectivity of NB33 for the eukaryotic decoding site. These results are therefore extremely beneficial for further research on both the design of new aminoglycoside-based antibiotics with diminished deleterious effects on humans, as well as the design of new aminoglycoside-based structures that selectively target the eukaryotic ribosome.

Differential selectivity of natural and synthetic aminoglycosides towards the eukaryotic and prokaryotic decoding A sites.,Kondo J, Hainrichson M, Nudelman I, Shallom-Shezifi D, Barbieri CM, Pilch DS, Westhof E, Baasov T Chembiochem. 2007 Sep 24;8(14):1700-9. PMID:17705310[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Kondo J, Hainrichson M, Nudelman I, Shallom-Shezifi D, Barbieri CM, Pilch DS, Westhof E, Baasov T. Differential selectivity of natural and synthetic aminoglycosides towards the eukaryotic and prokaryotic decoding A sites. Chembiochem. 2007 Sep 24;8(14):1700-9. PMID:17705310 doi:10.1002/cbic.200700271

2o3y, resolution 2.70Å

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