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| | <SX load='6az3' size='340' side='right' viewer='molstar' caption='[[6az3]], [[Resolution|resolution]] 2.50Å' scene=''> | | <SX load='6az3' size='340' side='right' viewer='molstar' caption='[[6az3]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6az3]] is a 50 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_donovani Leishmania donovani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AZ3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6az3]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_donovani Leishmania donovani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AZ3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PAR:PAROMOMYCIN'>PAR</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]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene>, <scene name='pdbligand=PAR:PAROMOMYCIN'>PAR</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6az1|6az1]]</div></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=6az3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6az3 OCA], [https://pdbe.org/6az3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6az3 RCSB], [https://www.ebi.ac.uk/pdbsum/6az3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6az3 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=6az3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6az3 OCA], [https://pdbe.org/6az3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6az3 RCSB], [https://www.ebi.ac.uk/pdbsum/6az3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6az3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/A0A3Q8ISR1_LEIDO A0A3Q8ISR1_LEIDO]] Component of the 60S subunit of the ribosome.[ARBA:ARBA00002241] exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-48-linked is involved in protein degradation via the proteasome. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[ARBA:ARBA00025328] [[https://www.uniprot.org/uniprot/RL37_LEIDO RL37_LEIDO]] Binds to the 23S rRNA.
| + | [https://www.uniprot.org/uniprot/A0A504XXD2_LEIDO A0A504XXD2_LEIDO] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Leishmania donovani]] | | [[Category: Leishmania donovani]] |
| - | [[Category: Bashan, A]] | + | [[Category: Bashan A]] |
| - | [[Category: Isobe, T]] | + | [[Category: Isobe T]] |
| - | [[Category: Jaffe, C L]] | + | [[Category: Jaffe CL]] |
| - | [[Category: Matzov, D]] | + | [[Category: Matzov D]] |
| - | [[Category: Nobe, Y]] | + | [[Category: Nobe Y]] |
| - | [[Category: Rozenberg, H]] | + | [[Category: Rozenberg H]] |
| - | [[Category: Shalev-Benami, M]] | + | [[Category: Shalev-Benami M]] |
| - | [[Category: Skiniotis, G]] | + | [[Category: Skiniotis G]] |
| - | [[Category: Taoka, M]] | + | [[Category: Taoka M]] |
| - | [[Category: Yonath, A]] | + | [[Category: Yonath A]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Zimmerman, E]] | + | [[Category: Zimmerman E]] |
| - | [[Category: Aminoglycoside]]
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| - | [[Category: Leishmania]]
| + | |
| - | [[Category: Paromomycin]]
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| - | [[Category: Ribosome]]
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| - | [[Category: Ribosome-antibiotic complex]]
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| Structural highlights
Function
A0A504XXD2_LEIDO
Publication Abstract from PubMed
Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite. We further show that PAR interferes with several aspects of cytosolic translation, thus highlighting the cytosolic rather than the mitochondrial ribosome as the primary drug target. The results also highlight unique as well as conserved elements in the PAR-binding pocket that can serve as hotspots for the development of novel therapeutics.
Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin.,Shalev-Benami M, Zhang Y, Rozenberg H, Nobe Y, Taoka M, Matzov D, Zimmerman E, Bashan A, Isobe T, Jaffe CL, Yonath A, Skiniotis G Nat Commun. 2017 Nov 17;8(1):1589. doi: 10.1038/s41467-017-01664-4. PMID:29150609[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shalev-Benami M, Zhang Y, Rozenberg H, Nobe Y, Taoka M, Matzov D, Zimmerman E, Bashan A, Isobe T, Jaffe CL, Yonath A, Skiniotis G. Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin. Nat Commun. 2017 Nov 17;8(1):1589. doi: 10.1038/s41467-017-01664-4. PMID:29150609 doi:http://dx.doi.org/10.1038/s41467-017-01664-4
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