5ndw: Difference between revisions
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==Crystal structure of aminoglycoside TC007 bound to the yeast 80S ribosome== | |||
<StructureSection load='5ndw' size='340' side='right'caption='[[5ndw]], [[Resolution|resolution]] 3.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ndw]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NDW 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]] 3.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8UZ:TC007'>8UZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5ndw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ndw OCA], [https://pdbe.org/5ndw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ndw RCSB], [https://www.ebi.ac.uk/pdbsum/5ndw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ndw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RS10A_YEAST RS10A_YEAST] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aminoglycosides are chemically diverse, broad-spectrum antibiotics that target functional centers within the bacterial ribosome to impact all four principle stages (initiation, elongation, termination, and recycling) of the translation mechanism. The propensity of aminoglycosides to induce miscoding errors that suppress the termination of protein synthesis supports their potential as therapeutic interventions in human diseases associated with premature termination codons (PTCs). However, the sites of interaction of aminoglycosides with the eukaryotic ribosome and their modes of action in eukaryotic translation remain largely unexplored. Here, we use the combination of X-ray crystallography and single-molecule FRET analysis to reveal the interactions of distinct classes of aminoglycosides with the 80S eukaryotic ribosome. Crystal structures of the 80S ribosome in complex with paromomycin, geneticin (G418), gentamicin, and TC007, solved at 3.3- to 3.7-A resolution, reveal multiple aminoglycoside-binding sites within the large and small subunits, wherein the 6'-hydroxyl substituent in ring I serves as a key determinant of binding to the canonical eukaryotic ribosomal decoding center. Multivalent binding interactions with the human ribosome are also evidenced through their capacity to affect large-scale conformational dynamics within the pretranslocation complex that contribute to multiple aspects of the translation mechanism. The distinct impacts of the aminoglycosides examined suggest that their chemical composition and distinct modes of interaction with the ribosome influence PTC read-through efficiency. These findings provide structural and functional insights into aminoglycoside-induced impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action beyond decoding. | |||
Aminoglycoside interactions and impacts on the eukaryotic ribosome.,Prokhorova I, Altman RB, Djumagulov M, Shrestha JP, Urzhumtsev A, Ferguson A, Chang CT, Yusupov M, Blanchard SC, Yusupova G Proc Natl Acad Sci U S A. 2017 Dec 5. pii: 1715501114. doi:, 10.1073/pnas.1715501114. PMID:29208708<ref>PMID:29208708</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ndw" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Djumagulov | ==See Also== | ||
[[Category: Urzhumtsev | *[[Ribosome 3D structures|Ribosome 3D structures]] | ||
[[Category: Yusupova | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | |||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Djumagulov M]] | |||
[[Category: Prokhorova I]] | |||
[[Category: Urzhumtsev A]] | |||
[[Category: Yusupov M]] | |||
[[Category: Yusupova G]] | |||
Latest revision as of 15:49, 15 November 2023
Crystal structure of aminoglycoside TC007 bound to the yeast 80S ribosomeCrystal structure of aminoglycoside TC007 bound to the yeast 80S ribosome
Structural highlights
FunctionPublication Abstract from PubMedAminoglycosides are chemically diverse, broad-spectrum antibiotics that target functional centers within the bacterial ribosome to impact all four principle stages (initiation, elongation, termination, and recycling) of the translation mechanism. The propensity of aminoglycosides to induce miscoding errors that suppress the termination of protein synthesis supports their potential as therapeutic interventions in human diseases associated with premature termination codons (PTCs). However, the sites of interaction of aminoglycosides with the eukaryotic ribosome and their modes of action in eukaryotic translation remain largely unexplored. Here, we use the combination of X-ray crystallography and single-molecule FRET analysis to reveal the interactions of distinct classes of aminoglycosides with the 80S eukaryotic ribosome. Crystal structures of the 80S ribosome in complex with paromomycin, geneticin (G418), gentamicin, and TC007, solved at 3.3- to 3.7-A resolution, reveal multiple aminoglycoside-binding sites within the large and small subunits, wherein the 6'-hydroxyl substituent in ring I serves as a key determinant of binding to the canonical eukaryotic ribosomal decoding center. Multivalent binding interactions with the human ribosome are also evidenced through their capacity to affect large-scale conformational dynamics within the pretranslocation complex that contribute to multiple aspects of the translation mechanism. The distinct impacts of the aminoglycosides examined suggest that their chemical composition and distinct modes of interaction with the ribosome influence PTC read-through efficiency. These findings provide structural and functional insights into aminoglycoside-induced impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action beyond decoding. Aminoglycoside interactions and impacts on the eukaryotic ribosome.,Prokhorova I, Altman RB, Djumagulov M, Shrestha JP, Urzhumtsev A, Ferguson A, Chang CT, Yusupov M, Blanchard SC, Yusupova G Proc Natl Acad Sci U S A. 2017 Dec 5. pii: 1715501114. doi:, 10.1073/pnas.1715501114. PMID:29208708[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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