4u50: Difference between revisions

Latest revision as of 16:49, 25 September 2026

Crystal structure of Verrucarin bound to the yeast 80S ribosome

Structural highlights

4u50 is a 19 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:	3L2, MG, OHX, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2]

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^[3]

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

References

↑ Ford CL, Randal-Whitis L, Ellis SR. Yeast proteins related to the p40/laminin receptor precursor are required for 20S ribosomal RNA processing and the maturation of 40S ribosomal subunits. Cancer Res. 1999 Feb 1;59(3):704-10. PMID:9973221
↑ Tabb-Massey A, Caffrey JM, Logsden P, Taylor S, Trent JO, Ellis SR. Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic Acids Res. 2003 Dec 1;31(23):6798-805. PMID:14627813
↑ 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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Ford CL, Randal-Whitis L, Ellis SR. Yeast proteins related to the p40/laminin receptor precursor are required for 20S ribosomal RNA processing and the maturation of 40S ribosomal subunits. Cancer Res. 1999 Feb 1;59(3):704-10. PMID:9973221

[2] Tabb-Massey A, Caffrey JM, Logsden P, Taylor S, Trent JO, Ellis SR. Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic Acids Res. 2003 Dec 1;31(23):6798-805. PMID:14627813

[3] 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]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='4u50' size='340' side='right'caption='[[4u50]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u50]] 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=4ulp 4ulp], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ulq 4ulq], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ulr 4ulr], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4uls 4uls] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4ult 4ult]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U50 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u50]] is a 19 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=4U50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U50 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3L2:(4S,5R,10E,12Z,16R,16aS,17S,18R,19aR,23aR)-4-hydroxy-5,16a,21-trimethyl-4,5,6,7,16,16a,22,23-octahydro-3H,18H,19aH-spiro[16,18-methano[1,6,12]trioxacyclooctadecino[3,4-d]chromene-17,2-oxirane]-3,9,14-trione'>3L2</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>
+</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=3L2:(4S,5R,10E,12Z,16R,16aS,17S,18R,19aR,23aR)-4-hydroxy-5,16a,21-trimethyl-4,5,6,7,16,16a,22,23-octahydro-3H,18H,19aH-spiro[16,18-methano[1,6,12]trioxacyclooctadecino[3,4-d]chromene-17,2-oxirane]-3,9,14-trione'>3L2</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>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4u50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u50 OCA], [https://pdbe.org/4u50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u50 RCSB], [https://www.ebi.ac.uk/pdbsum/4u50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u50 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/RL23A_YEAST RL23A_YEAST]
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 21: @@
 ==See Also==
+*[[Ribosome 3D structures|Ribosome 3D structures]]
 *[[3D sructureseceptor for activated protein kinase C 1|3D sructureseceptor for activated protein kinase C 1]]
 == References ==

4u50: Difference between revisions

Latest revision as of 16:49, 25 September 2026

Crystal structure of Verrucarin bound to the yeast 80S ribosome

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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