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- EMDB-53067: Cryo-EM structure of the A2085-methylated 50S ribosome of a MLSb ... -
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Open data
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Basic information
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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 | |||||||||
![]() | Postprocessed map of the focused refinement of the large ribosomal subunit obtained after Multibody refinement in Relion | |||||||||
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![]() | RIBOSOME | |||||||||
Function / homology | ![]() 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 ...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 | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.08 Å | |||||||||
![]() | Rivalta A / Yonath A | |||||||||
Funding support | 1 items
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![]() | ![]() Title: 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. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 28.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 50.4 KB 50.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 15.5 KB | Display | ![]() |
Images | ![]() | 53.6 KB | ||
Filedesc metadata | ![]() | 11.1 KB | ||
Others | ![]() ![]() | 235.9 MB 235.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 841 KB | Display | ![]() |
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Full document | ![]() | 840.5 KB | Display | |
Data in XML | ![]() | 23.1 KB | Display | |
Data in CIF | ![]() | 30.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9qehMC ![]() 9qegC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Postprocessed map of the focused refinement of the large ribosomal subunit obtained after Multibody refinement in Relion | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half-map 2 of the focused refinement of the large subunit
File | emd_53067_half_map_1.map | ||||||||||||
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Annotation | Half-map 2 of the focused refinement of the large subunit | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map 1 of the focused refinement of the large subunit
File | emd_53067_half_map_2.map | ||||||||||||
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Annotation | Half-map 1 of the focused refinement of the large subunit | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : A2085-methylated 50S ribosome of a MLSb resistant S. aureus strai...
+Supramolecule #1: A2085-methylated 50S ribosome of a MLSb resistant S. aureus strai...
+Macromolecule #1: Large ribosomal subunit protein bL33A
+Macromolecule #2: Large ribosomal subunit protein bL34
+Macromolecule #3: Large ribosomal subunit protein bL35
+Macromolecule #4: Large ribosomal subunit protein bL36
+Macromolecule #5: Large ribosomal subunit protein bL17
+Macromolecule #8: Large ribosomal subunit protein uL2
+Macromolecule #9: Large ribosomal subunit protein uL3
+Macromolecule #10: Large ribosomal subunit protein uL4
+Macromolecule #11: Large ribosomal subunit protein uL5
+Macromolecule #12: Large ribosomal subunit protein uL6
+Macromolecule #13: Large ribosomal subunit protein uL13
+Macromolecule #14: Large ribosomal subunit protein uL14
+Macromolecule #15: Large ribosomal subunit protein uL15
+Macromolecule #16: Large ribosomal subunit protein uL16
+Macromolecule #17: Large ribosomal subunit protein uL18
+Macromolecule #18: Large ribosomal subunit protein bL19
+Macromolecule #19: Large ribosomal subunit protein bL20
+Macromolecule #20: Large ribosomal subunit protein bL21
+Macromolecule #21: Large ribosomal subunit protein uL22
+Macromolecule #22: Large ribosomal subunit protein uL23
+Macromolecule #23: Large ribosomal subunit protein uL24
+Macromolecule #24: 50S ribosomal protein L25
+Macromolecule #25: Large ribosomal subunit protein bL27
+Macromolecule #26: Large ribosomal subunit protein bL28
+Macromolecule #27: Large ribosomal subunit protein uL29
+Macromolecule #28: Large ribosomal subunit protein uL30
+Macromolecule #29: Large ribosomal subunit protein bL32
+Macromolecule #6: 23S rRNA
+Macromolecule #7: 5S rRNA
+Macromolecule #30: P_site tRNA
+Macromolecule #31: E_site tRNA
+Macromolecule #32: ZINC ION
+Macromolecule #33: MAGNESIUM ION
+Macromolecule #34: (3aS,4R,7S,9R,10R,11R,13R,15R,15aR)-1-{4-[4-(3-aminophenyl)-1H-1,...
+Macromolecule #35: POTASSIUM ION
+Macromolecule #36: water
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |