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Yorodumi- PDB-9qeh: Cryo-EM structure of the A2085-methylated 50S ribosome of a MLSb ... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9qeh | ||||||
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| Title | Cryo-EM structure of the A2085-methylated 50S ribosome of a MLSb resistant S. aureus strain "MNY196" in complex with solithromycin | ||||||
Components |
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Keywords | RIBOSOME | ||||||
| Function / homology | Function and homology informationlarge ribosomal subunit / transferase activity / 5S rRNA binding / ribosomal large subunit assembly / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / negative regulation of translation / rRNA binding ...large ribosomal subunit / transferase activity / 5S rRNA binding / ribosomal large subunit assembly / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / negative regulation of translation / rRNA binding / structural constituent of ribosome / ribosome / translation / ribonucleoprotein complex / mRNA binding / cytoplasm Similarity search - Function | ||||||
| Biological species | Staphylococcus aureus subsp. aureus USA300 (bacteria) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.08 Å | ||||||
Authors | Rivalta, A. / Yonath, A. | ||||||
| Funding support | 1items
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Citation | Journal: Life Sci Alliance / Year: 2025Title: Structural studies on ribosomes of differentially macrolide-resistant strains. Authors: André Rivalta / Aliza Fedorenko / Alexandre Le Scornet / Sophie Thompson / Yehuda Halfon / Elinor Breiner Goldstein / Sude Çavdaroglu / Tal Melenitzky / Disha-Gajanan Hiregange / Ella ...Authors: André Rivalta / Aliza Fedorenko / Alexandre Le Scornet / Sophie Thompson / Yehuda Halfon / Elinor Breiner Goldstein / Sude Çavdaroglu / Tal Melenitzky / Disha-Gajanan Hiregange / Ella Zimmerman / Anat Bashan / Mee-Ngan Frances Yap / Ada Yonath / ![]() Abstract: Antimicrobial resistance is a major global health challenge, diminishing the efficacy of many antibiotics, including macrolides. In , an opportunistic pathogen, macrolide resistance is primarily ...Antimicrobial resistance is a major global health challenge, diminishing the efficacy of many antibiotics, including macrolides. In , an opportunistic pathogen, macrolide resistance is primarily mediated by Erm-family methyltransferases, which mono- or dimethylate A2058 in the 23S ribosomal RNA, reducing drug binding. Although macrolide-ribosome interactions have been characterized in nonpathogenic species, their structural basis in clinically relevant pathogens remains limited. In this study, we investigate the impact of -mediated resistance on drug binding by analyzing ribosomes from strains with varying levels of expression and activity. Using cryo-electron microscopy, we determined the high-resolution structures of solithromycin-bound ribosomes, including those with dimethylated A2058. Our structural analysis reveals the specific interactions that enable solithromycin binding despite double methylation and resistance, as corroborated by microbiological and biochemical data, suggesting that further optimization of ketolide-ribosome interactions could enhance macrolide efficacy against resistant strains. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9qeh.cif.gz | 2.6 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9qeh.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9qeh.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9qeh_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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| Full document | 9qeh_full_validation.pdf.gz | 1.5 MB | Display | |
| Data in XML | 9qeh_validation.xml.gz | 133.2 KB | Display | |
| Data in CIF | 9qeh_validation.cif.gz | 236.4 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qe/9qeh ftp://data.pdbj.org/pub/pdb/validation_reports/qe/9qeh | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 53067MC ![]() 9qegC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Assembly
| Deposited unit | ![]()
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Components
+Large ribosomal subunit protein ... , 26 types, 26 molecules 1234LCDEFGHIJKMNOPQRSUVWXZ
-RNA chain , 4 types, 4 molecules AB811
| #6: RNA chain | Mass: 946850.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus subsp. aureus USA300 (bacteria) |
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| #7: RNA chain | Mass: 36974.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus subsp. aureus USA300 (bacteria)References: GenBank: 1760048038 |
| #30: RNA chain | Mass: 22969.725 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus subsp. aureus USA300 (bacteria) |
| #31: RNA chain | Mass: 4170.574 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus subsp. aureus USA300 (bacteria) |
-Protein , 1 types, 1 molecules T
| #24: Protein | Mass: 23810.609 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus subsp. aureus USA300 (bacteria)References: UniProt: Q2FJE0 |
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-Non-polymers , 5 types, 912 molecules 








| #32: Chemical | | #33: Chemical | ChemComp-MG / #34: Chemical | ChemComp-EM1 / ( | #35: Chemical | ChemComp-K / #36: Water | ChemComp-HOH / | |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | N |
-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: A2085-methylated 50S ribosome of a MLSb resistant S. aureus strain "MNY196" in complex with solithromycin Type: RIBOSOME / Entity ID: #1-#31 / Source: NATURAL |
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| Source (natural) | Organism: Staphylococcus aureus subsp. aureus USA300 (bacteria) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid material: COPPER / Grid type: Quantifoil R2/2 |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 500 nm |
| Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.08 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 263087 Details: Resolution refers to gold-standard FSC 0.143 cutoff calculated on the postprocessed, solvent mask map Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
| Displacement parameters | Biso mean: 24.94 Å2 | ||||||||||||||||||||||||
| Refine LS restraints |
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Staphylococcus aureus subsp. aureus USA300 (bacteria)
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FIELD EMISSION GUN