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6qul
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6qul is ON HOLD Authors: Scaiola, A., Leibundgut, M., Boehringer, D., Ritz, D. Description: Structure of a bacterial 50S ribosomal subunit in compl...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of a bacterial 50S ribosomal subunit in complex with the novel quinoxolidinone antibiotic cadazolid== | |
| + | <SX load='6qul' size='340' side='right' viewer='molstar' caption='[[6qul]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6qul]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QUL 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]] 3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</scene>, <scene name='pdbligand=JJH:1-cyclopropyl-6-fluoranyl-7-[4-[[2-fluoranyl-4-[(5~{R})-5-(hydroxymethyl)-2-oxidanylidene-1,3-oxazolidin-3-yl]phenoxy]methyl]-4-oxidanyl-piperidin-1-yl]-4-oxidanylidene-quinoline-3-carboxylic+acid'>JJH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6qul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qul OCA], [https://pdbe.org/6qul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qul RCSB], [https://www.ebi.ac.uk/pdbsum/6qul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qul ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RL2_ECOLI RL2_ECOLI] One of the primary rRNA binding proteins. Located near the base of the L1 stalk, it is probably also mobile. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is highly controversial.[HAMAP-Rule:MF_01320_B] In the E.coli 70S ribosome in the initiation state it has been modeled to make several contacts with the 16S rRNA (forming bridge B7b, PubMed:12809609); these contacts are broken in the model with bound EF-G.[HAMAP-Rule:MF_01320_B] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Oxazolidinones are synthetic antibiotics used for treatment of infections caused by Gram-positive bacteria. They target the bacterial protein synthesis machinery by binding to the peptidyl transferase centre (PTC) of the ribosome and interfering with the peptidyl transferase reaction. Cadazolid is the first member of quinoxolidinone antibiotics, which are characterized by combining the pharmacophores of oxazolidinones and fluoroquinolones, and it is evaluated for treatment of Clostridium difficile gastrointestinal infections that frequently occur in hospitalized patients. In vitro protein synthesis inhibition by cadazolid was shown in Escherichia coli and Staphylococcus aureus, including an isolate resistant against linezolid, the prototypical oxazolidinone antibiotic. To better understand the mechanism of inhibition, we determined a 3.0 A cryo-electron microscopy structure of cadazolid bound to the E. coli ribosome in complex with mRNA and initiator tRNA. Here we show that cadazolid binds with its oxazolidinone moiety in a binding pocket in close vicinity of the PTC as observed previously for linezolid, and that it extends its unique fluoroquinolone moiety towards the A-site of the PTC. In this position, the drug inhibits protein synthesis by interfering with the binding of tRNA to the A-site, suggesting that its chemical features also can enable the inhibition of linezolid-resistant strains. | ||
| - | + | Structural basis of translation inhibition by cadazolid, a novel quinoxolidinone antibiotic.,Scaiola A, Leibundgut M, Boehringer D, Caspers P, Bur D, Locher HH, Rueedi G, Ritz D Sci Rep. 2019 Apr 4;9(1):5634. doi: 10.1038/s41598-019-42155-4. PMID:30948752<ref>PMID:30948752</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6qul" style="background-color:#fffaf0;"></div> |
| - | [[Category: Leibundgut | + | |
| - | [[Category: Ritz | + | ==See Also== |
| - | [[Category: | + | *[[Ribosome 3D structures|Ribosome 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </SX> | ||
| + | [[Category: Escherichia coli]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Boehringer D]] | ||
| + | [[Category: Leibundgut M]] | ||
| + | [[Category: Ritz D]] | ||
| + | [[Category: Scaiola A]] | ||
Current revision
Structure of a bacterial 50S ribosomal subunit in complex with the novel quinoxolidinone antibiotic cadazolid
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