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==Cryo-EM structure of the small subunit of Leishmania ribosome bound to paromomycin== | |||
<SX load='6az1' size='340' side='right' viewer='molstar' caption='[[6az1]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6az1]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Leishmania_donovani Leishmania donovani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AZ1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OC:4N,O2-METHYLCYTIDINE-5-MONOPHOSPHATE'>4OC</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=7MG:7N-METHYL-8-HYDROGUANOSINE-5-MONOPHOSPHATE'>7MG</scene>, <scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=C4J:(5S)-5-{3-[(3S)-3-amino-3-carboxypropyl]-1-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl}-2,5-anhydro-1-O-phosphono-L-arabinitol'>C4J</scene>, <scene name='pdbligand=M1Y:[(2~{R},3~{R},4~{R},5~{S})-5-[1-methyl-2,4-bis(oxidanylidene)pyrimidin-5-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>M1Y</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MIA:2-METHYLTHIO-N6-ISOPENTENYL-ADENOSINE-5-MONOPHOSPHATE'>MIA</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6az1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6az1 OCA], [https://pdbe.org/6az1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6az1 RCSB], [https://www.ebi.ac.uk/pdbsum/6az1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6az1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/E9BRS2_LEIDO E9BRS2_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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6az1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ribosome 3D structures|Ribosome 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</SX> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Leishmania donovani]] | |||
[[Category: Bashan A]] | |||
[[Category: Jaffe CL]] | |||
[[Category: Matzov D]] | |||
[[Category: Rozenberg H]] | |||
[[Category: Shalev-Benami M]] | |||
[[Category: Skiniotis G]] | |||
[[Category: Yonath A]] | |||
[[Category: Zhang Y]] | |||
[[Category: Zimmerman E]] | |||
Latest revision as of 15:26, 6 November 2024
Cryo-EM structure of the small subunit of Leishmania ribosome bound to paromomycinCryo-EM structure of the small subunit of Leishmania ribosome bound to paromomycin
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