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{{Large structure}}
 
==Cryo-EM structure of of the large subunit of Leishmania ribosome bound to paromomycin==
==Cryo-EM structure of of the large subunit of Leishmania ribosome bound to paromomycin==
<StructureSection load='6az3' size='340' side='right' caption='[[6az3]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<SX load='6az3' size='340' side='right' viewer='molstar' caption='[[6az3]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6az3]] is a 50 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/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"><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]] 2.5&#8491;</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">[[6az1|6az1]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6az3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6az3 OCA], [http://pdbe.org/6az3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6az3 RCSB], [http://www.ebi.ac.uk/pdbsum/6az3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6az3 ProSAT]</span></td></tr>
</table>
</table>
{{Large structure}}
== Function ==
== Function ==
[[http://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;">
== 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<ref>PMID:29150609</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6az3" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Ribosome 3D structures|Ribosome 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</SX>
[[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]]
[[Category: Leishmania]]
[[Category: Paromomycin]]
[[Category: Ribosome]]
[[Category: Ribosome-antibiotic complex]]
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