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Yorodumi- EMDB-4641: Structure of a bacterial 70S ribosomal subunit in complex with ca... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4641 | |||||||||
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Title | Structure of a bacterial 70S ribosomal subunit in complex with cadazolid, reconstruction focused around the 30S ribosomal subunit | |||||||||
Map data | ||||||||||
Sample |
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Biological species | Escherichia coli (E. coli) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Scaiola A / Leibundgut M / Boehringer D / Ritz D | |||||||||
Citation | Journal: Sci Rep / Year: 2019 Title: Structural basis of translation inhibition by cadazolid, a novel quinoxolidinone antibiotic. Authors: Alain Scaiola / Marc Leibundgut / Daniel Boehringer / Patrick Caspers / Daniel Bur / Hans H Locher / Georg Rueedi / Daniel Ritz / Abstract: 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 ...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 Å 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. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4641.map.gz | 11.9 MB | EMDB map data format | |
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Header (meta data) | emd-4641-v30.xml emd-4641.xml | 17.5 KB 17.5 KB | Display Display | EMDB header |
Images | emd_4641.png | 129.7 KB | ||
Masks | emd_4641_msk_1.map | 244.1 MB | Mask map | |
Others | emd_4641_half_map_1.map.gz emd_4641_half_map_2.map.gz | 192.6 MB 192.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4641 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4641 | HTTPS FTP |
-Validation report
Summary document | emd_4641_validation.pdf.gz | 385.4 KB | Display | EMDB validaton report |
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Full document | emd_4641_full_validation.pdf.gz | 384.2 KB | Display | |
Data in XML | emd_4641_validation.xml.gz | 494 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4641 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4641 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4641.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.079 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_4641_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_4641_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_4641_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Structure of a bacterial 70S ribosomal subunit in complex with ca...
Entire | Name: Structure of a bacterial 70S ribosomal subunit in complex with cadazolid, reconstruction focused around the 30S ribosomal subunit |
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Components |
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-Supramolecule #1: Structure of a bacterial 70S ribosomal subunit in complex with ca...
Supramolecule | Name: Structure of a bacterial 70S ribosomal subunit in complex with cadazolid, reconstruction focused around the 30S ribosomal subunit type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#31 |
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Source (natural) | Organism: Escherichia coli (E. coli) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Detector mode: INTEGRATING / Average electron dose: 1.14 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |