4u6f: Difference between revisions
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''' | ==Crystal structure of T-2 toxin bound to the yeast 80S ribosome== | ||
<StructureSection load='4u6f' size='340' side='right' caption='[[4u6f]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4u6f]] is a 162 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_atcc_204508_/_s288c Saccharomyces cerevisiae atcc 204508 / s288c]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujy 4ujy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U6F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U6F FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OHX:OSMIUM+(III)+HEXAMMINE'>OHX</scene>, <scene name='pdbligand=ZBA:12,13-EPOXYTRICHOTHEC-9-ENE-3,4,8,15-TETROL-4,15-DIACETATE-8-ISOVALERATE'>ZBA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uju|4uju]], [[4ujv|4ujv]], [[4ujw|4ujw]], [[4ujx|4ujx]], [[4ujy|4ujy]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u6f RCSB], [http://www.ebi.ac.uk/pdbsum/4u6f PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development. | |||
Structural basis for the inhibition of the eukaryotic ribosome.,Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10. PMID:25209664<ref>PMID:25209664</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Ribosome 3D structures|Ribosome 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Saccharomyces cerevisiae atcc 204508 / s288c]] | |||
[[Category: Loubresse, N Garreau de]] | |||
[[Category: Prokhorova, I]] | |||
[[Category: Yusupov, M]] | |||
[[Category: Yusupova, G]] | |||
[[Category: Antibiotic]] | |||
[[Category: Eukaryote]] | |||
[[Category: Inhibitor]] | |||
[[Category: Ribosome]] | |||
[[Category: Rna-protein complex]] | |||
[[Category: Translation]] | |||
Revision as of 13:18, 17 December 2014
Crystal structure of T-2 toxin bound to the yeast 80S ribosomeCrystal structure of T-2 toxin bound to the yeast 80S ribosome
Structural highlights
Publication Abstract from PubMedThe ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development. Structural basis for the inhibition of the eukaryotic ribosome.,Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10. PMID:25209664[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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