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Yorodumi- PDB-6qul: Structure of a bacterial 50S ribosomal subunit in complex with th... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6qul | ||||||
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Title | Structure of a bacterial 50S ribosomal subunit in complex with the novel quinoxolidinone antibiotic cadazolid | ||||||
Components |
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Keywords | ANTIBIOTIC / ribosome / cadazolid / quinoxolidinone / 50S | ||||||
Function / homology | Function and homology information transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / positive regulation of ribosome biogenesis / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / mRNA regulatory element binding translation repressor activity / ribosome assembly ...transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / positive regulation of ribosome biogenesis / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / mRNA regulatory element binding translation repressor activity / ribosome assembly / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / ribosomal large subunit assembly / response to reactive oxygen species / regulation of cell growth / DNA-templated transcription termination / response to radiation / mRNA 5'-UTR binding / large ribosomal subunit / ribosome binding / transferase activity / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / translation / response to antibiotic / negative regulation of DNA-templated transcription / mRNA binding / DNA binding / RNA binding / zinc ion binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Escherichia coli (E. coli) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6qul.cif.gz | 1.9 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6qul.ent.gz | 1.5 MB | Display | PDB format |
PDBx/mmJSON format | 6qul.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6qul_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 6qul_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 6qul_validation.xml.gz | 127.6 KB | Display | |
Data in CIF | 6qul_validation.cif.gz | 216.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qu/6qul ftp://data.pdbj.org/pub/pdb/validation_reports/qu/6qul | HTTPS FTP |
-Related structure data
Related structure data | 4638MC 4639C 4641C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 3 types, 3 molecules 1AB
#1: RNA chain | Mass: 1223.818 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) |
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#2: RNA chain | Mass: 906514.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) |
#3: RNA chain | Mass: 38790.090 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 1476653947 |
+50S ribosomal protein ... , 28 types, 28 molecules CDEFGHKLMNOPQRSTUVWXYZabcdef
-Non-polymers , 5 types, 386 molecules
#32: Chemical | ChemComp-FME / | ||||||
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#33: Chemical | ChemComp-MG / #34: Chemical | ChemComp-A / | #35: Chemical | ChemComp-JJH / | #36: Chemical | ChemComp-ZN / | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Structure of a bacterial 50S ribosomal subunit in complex with the novel quinoxolidinone antibiotic cadazolid Type: RIBOSOME / Entity ID: #1-#31 / Source: NATURAL |
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Molecular weight | Units: MEGADALTONS / Experimental value: NO |
Source (natural) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid type: Quantifoil R2/2 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.14 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 59148 / Symmetry type: POINT |