4u51: Difference between revisions

Latest revision as of 16:50, 25 September 2026

Crystal structure of Narciclasine bound to the yeast 80S ribosome

Structural highlights

4u51 is a 20 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:	3KF, MG, OHX, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RS22A_YEAST

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^[1]

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

References

↑ Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M. Structural basis for the inhibition of the eukaryotic ribosome. Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10. PMID:25209664 doi:https://dx.doi.org/10.1038/nature13737

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OCA

[1] Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M. Structural basis for the inhibition of the eukaryotic ribosome. Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10. PMID:25209664 doi:https://dx.doi.org/10.1038/nature13737

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='4u51' size='340' side='right'caption='[[4u51]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u51]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujf 4ujf], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujg 4ujg], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujh 4ujh], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4uji 4uji] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ujj 4ujj]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U51 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u51]] is a 20 chain structure with sequence from [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=4U51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U51 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]] 3.2&#8491;</td></tr>
 <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3KF:(2S,3R,4S,4AR)-2,3,4,7-TETRAHYDROXY-3,4,4A,5-TETRAHYDRO[1,3]DIOXOLO[4,5-J]PHENANTHRIDIN-6(2H)-ONE'>3KF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OHX:OSMIUM+(III)+HEXAMMINE'>OHX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
@@ Line 9: / Line 9: @@
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/RSSA1_YEAST RSSA1_YEAST] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits.<ref>PMID:9973221</ref> <ref>PMID:14627813</ref>
+[https://www.uniprot.org/uniprot/RS22A_YEAST RS22A_YEAST]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4u51: Difference between revisions

Latest revision as of 16:50, 25 September 2026

Crystal structure of Narciclasine bound to the yeast 80S ribosome

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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