+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26819 | |||||||||
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Title | A. baumannii 70S ribosome-Streptothricin-F complex | |||||||||
Map data | A baumannii 70S ribosome-SF complex | |||||||||
Sample |
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Keywords | Streptothricin / Nourseothricin / Antibiotic / Ribosome / Ribosome-RNA complex | |||||||||
Function / homology | Function and homology information ribosomal small subunit biogenesis / small ribosomal subunit rRNA binding / large ribosomal subunit / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / transferase activity / cytosolic small ribosomal subunit / ribosomal large subunit assembly ...ribosomal small subunit biogenesis / small ribosomal subunit rRNA binding / large ribosomal subunit / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / transferase activity / cytosolic small ribosomal subunit / ribosomal large subunit assembly / cytoplasmic translation / cytosolic large ribosomal subunit / tRNA binding / negative regulation of translation / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / RNA binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Acinetobacter baumannii AB0057 (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.35 Å | |||||||||
Authors | Morgan CE / Yu EW | |||||||||
Funding support | United States, 1 items
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Citation | Journal: PLoS Biol / Year: 2023 Title: Streptothricin F is a bactericidal antibiotic effective against highly drug-resistant gram-negative bacteria that interacts with the 30S subunit of the 70S ribosome. Authors: Christopher E Morgan / Yoon-Suk Kang / Alex B Green / Kenneth P Smith / Matthew G Dowgiallo / Brandon C Miller / Lucius Chiaraviglio / Katherine A Truelson / Katelyn E Zulauf / Shade ...Authors: Christopher E Morgan / Yoon-Suk Kang / Alex B Green / Kenneth P Smith / Matthew G Dowgiallo / Brandon C Miller / Lucius Chiaraviglio / Katherine A Truelson / Katelyn E Zulauf / Shade Rodriguez / Anthony D Kang / Roman Manetsch / Edward W Yu / James E Kirby / Abstract: The streptothricin natural product mixture (also known as nourseothricin) was discovered in the early 1940s, generating intense initial interest because of excellent gram-negative activity. Here, we ...The streptothricin natural product mixture (also known as nourseothricin) was discovered in the early 1940s, generating intense initial interest because of excellent gram-negative activity. Here, we establish the activity spectrum of nourseothricin and its main components, streptothricin F (S-F, 1 lysine) and streptothricin D (S-D, 3 lysines), purified to homogeneity, against highly drug-resistant, carbapenem-resistant Enterobacterales (CRE) and Acinetobacter baumannii. For CRE, the MIC50 and MIC90 for S-F and S-D were 2 and 4 μM, and 0.25 and 0.5 μM, respectively. S-F and nourseothricin showed rapid, bactericidal activity. S-F and S-D both showed approximately 40-fold greater selectivity for prokaryotic than eukaryotic ribosomes in in vitro translation assays. In vivo, delayed renal toxicity occurred at >10-fold higher doses of S-F compared with S-D. Substantial treatment effect of S-F in the murine thigh model was observed against the otherwise pandrug-resistant, NDM-1-expressing Klebsiella pneumoniae Nevada strain with minimal or no toxicity. Cryo-EM characterization of S-F bound to the A. baumannii 70S ribosome defines extensive hydrogen bonding of the S-F steptolidine moiety, as a guanine mimetic, to the 16S rRNA C1054 nucleobase (Escherichia coli numbering) in helix 34, and the carbamoylated gulosamine moiety of S-F with A1196, explaining the high-level resistance conferred by corresponding mutations at the residues identified in single rrn operon E. coli. Structural analysis suggests that S-F probes the A-decoding site, which potentially may account for its miscoding activity. Based on unique and promising activity, we suggest that the streptothricin scaffold deserves further preclinical exploration as a potential therapeutic for drug-resistant, gram-negative pathogens. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26819.map.gz | 21.5 MB | EMDB map data format | |
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Header (meta data) | emd-26819-v30.xml emd-26819.xml | 64.2 KB 64.2 KB | Display Display | EMDB header |
Images | emd_26819.png | 125.7 KB | ||
Filedesc metadata | emd-26819.cif.gz | 13.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26819 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26819 | HTTPS FTP |
-Validation report
Summary document | emd_26819_validation.pdf.gz | 450.6 KB | Display | EMDB validaton report |
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Full document | emd_26819_full_validation.pdf.gz | 450.2 KB | Display | |
Data in XML | emd_26819_validation.xml.gz | 7.9 KB | Display | |
Data in CIF | emd_26819_validation.cif.gz | 9.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26819 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26819 | HTTPS FTP |
-Related structure data
Related structure data | 7uvxMC 7uvvC 7uvwC 7uvyC 7uvzC 7uw1C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26819.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | A baumannii 70S ribosome-SF complex | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.848 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : SF-70S Ribosome Complex
+Supramolecule #1: SF-70S Ribosome Complex
+Macromolecule #1: 50S ribosomal protein L33
+Macromolecule #2: 50S ribosomal protein L34
+Macromolecule #3: 50S ribosomal protein L35
+Macromolecule #4: 50S ribosomal protein L36
+Macromolecule #7: 50S ribosomal protein L2
+Macromolecule #8: 50S ribosomal protein L3
+Macromolecule #9: 50S ribosomal protein L4
+Macromolecule #10: 50S ribosomal protein L5
+Macromolecule #11: 50S ribosomal protein L6
+Macromolecule #12: 50S ribosomal protein L9
+Macromolecule #13: 50S ribosomal protein L13
+Macromolecule #14: 50S ribosomal protein L14
+Macromolecule #15: 50S ribosomal protein L15
+Macromolecule #16: 50S ribosomal protein L16
+Macromolecule #17: 50S ribosomal protein L17
+Macromolecule #18: 50S ribosomal protein L18
+Macromolecule #19: 50S ribosomal protein L19
+Macromolecule #20: 50S ribosomal protein L20
+Macromolecule #21: 50S ribosomal protein L21
+Macromolecule #22: 50S ribosomal protein L22
+Macromolecule #23: 50S ribosomal protein L23
+Macromolecule #24: 50S ribosomal protein L24
+Macromolecule #25: 50S ribosomal protein L25
+Macromolecule #26: 50S ribosomal protein L27
+Macromolecule #27: 50S ribosomal protein L28
+Macromolecule #28: 50S ribosomal protein L29
+Macromolecule #29: 50S ribosomal protein L30
+Macromolecule #30: 50S ribosomal protein L32
+Macromolecule #32: 30S ribosomal protein S2
+Macromolecule #33: 30S ribosomal protein S3
+Macromolecule #34: 30S ribosomal protein S4
+Macromolecule #35: 30S ribosomal protein S5
+Macromolecule #36: 30S ribosomal protein S6
+Macromolecule #37: 30S ribosomal protein S7
+Macromolecule #38: 30S ribosomal protein S8
+Macromolecule #39: 30S ribosomal protein S9
+Macromolecule #40: 30S ribosomal protein S10
+Macromolecule #41: 30S ribosomal protein S11
+Macromolecule #42: 30S ribosomal protein S12
+Macromolecule #43: 30S ribosomal protein S13
+Macromolecule #44: 30S ribosomal protein S14
+Macromolecule #45: 30S ribosomal protein S15
+Macromolecule #46: 30S ribosomal protein S16
+Macromolecule #47: 30S ribosomal protein S17
+Macromolecule #48: 30S ribosomal protein S18
+Macromolecule #49: 30S ribosomal protein S19
+Macromolecule #50: 30S ribosomal protein S20
+Macromolecule #51: 30S ribosomal protein S21
+Macromolecule #5: 23s ribosomal RNA
+Macromolecule #6: 5s ribosomal RNA
+Macromolecule #31: 16s Ribosomal RNA
+Macromolecule #52: ZINC ION
+Macromolecule #53: Streptothricin F
-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 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL / In silico model: ab inito |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.35 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 135858 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |