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- PDB-7qq3: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7qq3 | ||||||
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Title | Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A. | ||||||
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![]() | RIBOSOME / Antibiotic / Myxovalargin A / MyxA | ||||||
Function / homology | ![]() 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 / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.1 Å | ||||||
![]() | Koller, T.O. / Beckert, B. / Wilson, D.N. | ||||||
Funding support | ![]()
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![]() | ![]() Title: The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition. Authors: Timm O Koller / Ullrich Scheid / Teresa Kösel / Jennifer Herrmann / Daniel Krug / Helena I M Boshoff / Bertrand Beckert / Joanna C Evans / Jan Schlemmer / Becky Sloan / Danielle M Weiner / ...Authors: Timm O Koller / Ullrich Scheid / Teresa Kösel / Jennifer Herrmann / Daniel Krug / Helena I M Boshoff / Bertrand Beckert / Joanna C Evans / Jan Schlemmer / Becky Sloan / Danielle M Weiner / Laura E Via / Atica Moosa / Thomas R Ioerger / Michael Graf / Boris Zinshteyn / Maha Abdelshahid / Fabian Nguyen / Stefan Arenz / Franziska Gille / Maik Siebke / Tim Seedorf / Oliver Plettenburg / Rachel Green / Anna-Luisa Warnke / Joachim Ullrich / Ralf Warrass / Clifton E Barry / Digby F Warner / Valerie Mizrahi / Andreas Kirschning / Daniel N Wilson / Rolf Müller / ![]() ![]() ![]() Abstract: Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum ...Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against . To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.9 MB | Display | ![]() |
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PDB format | ![]() | 1.5 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 14121MC ![]() 8b7yC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-RNA chain , 2 types, 2 molecules IJ
#1: RNA chain | Mass: 941752.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#2: RNA chain | Mass: 38815.098 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
+50S ribosomal protein ... , 26 types, 26 molecules KLMORSTUVWXYZabcdefghijklm
-Protein/peptide , 1 types, 1 molecules B
#29: Protein/peptide | Type: Peptide-like / Class: Antibiotic / Mass: 1678.092 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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-Non-polymers , 3 types, 174 molecules ![](data/chem/img/MG.gif)
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#30: Chemical | ChemComp-MG / #31: Chemical | ChemComp-ZN / | #32: Water | ChemComp-HOH / | |
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-Details
Compound details | PubChem CID 137628402 |
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Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A. Type: RIBOSOME / Entity ID: #1-#29 / Source: NATURAL | |||||||||||||||||||||||||||||||||||
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Molecular weight | Value: 1.356 MDa / Experimental value: NO | |||||||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | |||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 Details: Solutions were made fresh, pH was adjusted with potassium hydroxide at 4 degrees celcius and sterile filtered. | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: 7 OD(A260/mL) were applied to the grid. | |||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R3/3 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277 K / Details: 2 seconds blotting before plunging. |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 44 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
Image scans | Movie frames/image: 40 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 680054 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 580425 / Algorithm: FOURIER SPACE / Num. of class averages: 3 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Target criteria: Correlation coefficient | ||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 4YBB |