6i9r
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6i9r]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9R FirstGlance]. <br> | <table><tr><td colspan='2'>[[6i9r]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9R FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=004:(2S)-AMINO(PHENYL)ETHANOIC+ACID'>004</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MU:2,5-DIMETHYLURIDINE-5-MONOPHOSPHATE'>2MU</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene>, <scene name='pdbligand=H8T:Virginiamycin+M'>H8T</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MHT:(3S)-3-(METHYLSULFANYL)-1-AZABICYCLO[2.2.2]OCTANE'>MHT</scene>, <scene name='pdbligand=MHU:4-N,N-(DIMETHYLAMINO)-L-PHENYLALANINE'>MHU</scene>, <scene name='pdbligand=MHV:4-OXO-L-PIPECOLIC+ACID'>MHV</scene>, <scene name='pdbligand=MHW:3-HYDROXYPICOLINIC+ACID'>MHW</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">Electron Microscopy, [[Resolution|Resolution]] 3.9Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=004:(2S)-AMINO(PHENYL)ETHANOIC+ACID'>004</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MU:2,5-DIMETHYLURIDINE-5-MONOPHOSPHATE'>2MU</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene>, <scene name='pdbligand=H8T:Virginiamycin+M'>H8T</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MHT:(3S)-3-(METHYLSULFANYL)-1-AZABICYCLO[2.2.2]OCTANE'>MHT</scene>, <scene name='pdbligand=MHU:4-N,N-(DIMETHYLAMINO)-L-PHENYLALANINE'>MHU</scene>, <scene name='pdbligand=MHV:4-OXO-L-PIPECOLIC+ACID'>MHV</scene>, <scene name='pdbligand=MHW:3-HYDROXYPICOLINIC+ACID'>MHW</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=6i9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9r OCA], [https://pdbe.org/6i9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9r RCSB], [https://www.ebi.ac.uk/pdbsum/6i9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9r ProSAT]</span></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=6i9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9r OCA], [https://pdbe.org/6i9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9r RCSB], [https://www.ebi.ac.uk/pdbsum/6i9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/RM09_HUMAN RM09_HUMAN] | [https://www.uniprot.org/uniprot/RM09_HUMAN RM09_HUMAN] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment. | ||
| - | + | ==See Also== | |
| - | + | *[[Ribosome 3D structures|Ribosome 3D structures]] | |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 07:35, 1 May 2024
Large subunit of the human mitochondrial ribosome in complex with Virginiamycin M and Quinupristin
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