View source for 5mei


==Crystal structure of Agelastatin A bound to the 80S ribosome==
<StructureSection load='5mei' size='340' side='right'caption='[[5mei]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mei]] 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=5MEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MEI 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]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7MB:Agelastatin+A'>7MB</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=5mei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mei OCA], [https://pdbe.org/5mei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mei RCSB], [https://www.ebi.ac.uk/pdbsum/5mei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mei ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL2A_YEAST RL2A_YEAST] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein synthesis plays an essential role in cell proliferation, differentiation, and survival. Inhibitors of eukaryotic translation have entered the clinic, establishing the translation machinery as a promising target for chemotherapy. A recently discovered, structurally unique marine sponge-derived brominated alkaloid, (-)-agelastatin A (AglA), possesses potent antitumor activity. Its underlying mechanism of action, however, has remained unknown. Using a systematic top-down approach, we show that AglA selectively inhibits protein synthesis. Using a high-throughput chemical footprinting method, we mapped the AglA-binding site to the ribosomal A site. A 3.5 A crystal structure of the 80S eukaryotic ribosome from S. cerevisiae in complex with AglA was obtained, revealing multiple conformational changes of the nucleotide bases in the ribosome accompanying the binding of AglA. Together, these results have unraveled the mechanism of inhibition of eukaryotic translation by AglA at atomic level, paving the way for future structural modifications to develop AglA analogs into novel anticancer agents.

Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A.,McClary B, Zinshteyn B, Meyer M, Jouanneau M, Pellegrino S, Yusupova G, Schuller A, Reyes JCP, Lu J, Guo Z, Ayinde S, Luo C, Dang Y, Romo D, Yusupov M, Green R, Liu JO Cell Chem Biol. 2017 May 18;24(5):605-613.e5. doi:, 10.1016/j.chembiol.2017.04.006. Epub 2017 Apr 27. PMID:28457705<ref>PMID:28457705</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mei" style="background-color:#fffaf0;"></div>

==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 ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Dang Y]]
[[Category: Green R]]
[[Category: Jouanneau M]]
[[Category: Liu JO]]
[[Category: Lu J]]
[[Category: Luo C]]
[[Category: McClary B]]
[[Category: Meyer M]]
[[Category: Pellegrino S]]
[[Category: Reyes JCP]]
[[Category: Romo D]]
[[Category: Schuller A]]
[[Category: Yusupov M]]
[[Category: Yusupova G]]
[[Category: Zinshteyn B]]