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Yorodumi- EMDB-55145: Cryo-EM structure of SKM-70S ribosomal stalled complex in the rot... -
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Open data
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Basic information
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| Title | Cryo-EM structure of SKM-70S ribosomal stalled complex in the rotated state with hybrid tRNAs | |||||||||||||||
Map data | Main (postprocessed) map | |||||||||||||||
Sample |
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Keywords | Antibiotics / 70S complex / RIBOSOME | |||||||||||||||
| Function / homology | Function and homology informationnegative regulation of cytoplasmic translational initiation / transcription antitermination factor activity, RNA binding / ornithine decarboxylase inhibitor activity / misfolded RNA binding / Group I intron splicing / RNA folding / transcriptional attenuation / endoribonuclease inhibitor activity / positive regulation of ribosome biogenesis / RNA-binding transcription regulator activity ...negative regulation of cytoplasmic translational initiation / transcription antitermination factor activity, RNA binding / ornithine decarboxylase inhibitor activity / misfolded RNA binding / Group I intron splicing / RNA folding / transcriptional attenuation / endoribonuclease inhibitor activity / positive regulation of ribosome biogenesis / RNA-binding transcription regulator activity / negative regulation of cytoplasmic translation / four-way junction DNA binding / DnaA-L2 complex / translation repressor activity / negative regulation of translational initiation / regulation of mRNA stability / negative regulation of DNA-templated DNA replication initiation / mRNA regulatory element binding translation repressor activity / positive regulation of RNA splicing / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / response to reactive oxygen species / regulation of DNA-templated transcription elongation / ribosome assembly / transcription elongation factor complex / transcription antitermination / DNA endonuclease activity / regulation of cell growth / translational initiation / DNA-templated transcription termination / response to radiation / maintenance of translational fidelity / mRNA 5'-UTR binding / regulation of translation / large ribosomal subunit / ribosome biogenesis / transferase activity / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / ribosomal large subunit assembly / 5S rRNA binding / small ribosomal subunit / small ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / 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 / hydrolase activity / response to antibiotic / negative regulation of DNA-templated transcription / mRNA binding / DNA binding / RNA binding / zinc ion binding / membrane / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
| Biological species | ![]() Streptococcus sanguinis (bacteria) | |||||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||||||||
Authors | Morici M / Corazza M / Safdari HA / Wilson DN | |||||||||||||||
| Funding support | United States, Canada, Germany, 4 items
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Citation | Journal: Res Sq / Year: 2025Title: Saskemycin, a potent and selective antimycobacterial agent targeting a unique site on the ribosome. Authors: Gerard Wright / Michael Cook / Min Xu / Martino Morici / Dmitrii Travin / Wenliang Wang / Dorota Klepacki / Nandini Chhabra / Vishwas Rao / Henok Sahile / Dirk Hackenberger / Haaris Safdari ...Authors: Gerard Wright / Michael Cook / Min Xu / Martino Morici / Dmitrii Travin / Wenliang Wang / Dorota Klepacki / Nandini Chhabra / Vishwas Rao / Henok Sahile / Dirk Hackenberger / Haaris Safdari / Max Berger / Martina Corazza / Austin Bond / Allison Guitor / Dominique Tertigas / Lijun Wang / Adam Schaenzer / Linda Ejim / Venkateswarlu Yarlagadda / James Gomez / Michael Surette / Yossef Av-Gay / Neeraj Dhar / Deborah Hung / Nora Vázquez-Laslop / Alexander Mankin / Daniel Wilson / ![]() Abstract: Tuberculosis is the deadliest bacterial disease on the planet. The months-long regimen of multiple antibiotics required to treat tuberculosis profoundly affects the microbiome and leads to the ...Tuberculosis is the deadliest bacterial disease on the planet. The months-long regimen of multiple antibiotics required to treat tuberculosis profoundly affects the microbiome and leads to the development of antimicrobial resistance. Furthermore, non-tuberculous mycobacterial infections pose an increasing clinical challenge. Consequently, there is a growing need for new narrow-spectrum mycobacteria-targeting antibiotics with different mechanisms of action. Here, we report the discovery and characterization of a natural glycolipid antibiotic, saskemycin (SKM), which demonstrates potent and highly selective activity against mycobacteria. Genome sequencing, chemical analysis, and isotope feeding strategies reveal the unique structure and biosynthetic origin of SKM. SKM binds to the small ribosomal subunit at a site not targeted by any of the clinically relevant antibiotics acting on the ribosome. Bound to the ribosome, SKM corrupts the decoding center in a unique way, preventing stable binding of aminoacyl-tRNA in the A site and inhibiting translation in a sequence context-specific manner. Self-resistance in the producing organism is conferred by methylation of a single 16S rRNA nucleotide by SasO and SasN rRNA methyltransferases. These enzymes are orthologs of the ubiquitous RsmC and SpoU methyltransferases found in most bacterial genera but absent in mycobacteria, rationalizing SKM's exquisite selectivity. The discovery of SKM provides an entry point for the development of selective, microbiome-sparing antimycobacterial antibiotics with a unique structure, binding site, and mechanism of action. | |||||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_55145.map.gz | 41.9 MB | EMDB map data format | |
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| Header (meta data) | emd-55145-v30.xml emd-55145.xml | 74.7 KB 74.7 KB | Display Display | EMDB header |
| Images | emd_55145.png | 75.2 KB | ||
| Filedesc metadata | emd-55145.cif.gz | 15.2 KB | ||
| Others | emd_55145_half_map_1.map.gz emd_55145_half_map_2.map.gz | 263.7 MB 263.7 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-55145 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-55145 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9sroMC ![]() 9qqqC ![]() 9qsjC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_55145.map.gz / Format: CCP4 / Size: 307.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | Main (postprocessed) map | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: Half map 2, used to generate the main map upon postprocessing
| File | emd_55145_half_map_1.map | ||||||||||||
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| Annotation | Half map 2, used to generate the main map upon postprocessing | ||||||||||||
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| Density Histograms |
-Half map: Half map 1, used to generate the main map upon postprocessing
| File | emd_55145_half_map_2.map | ||||||||||||
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| Annotation | Half map 1, used to generate the main map upon postprocessing | ||||||||||||
| Projections & Slices |
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| Density Histograms |
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Sample components
+Entire : Cryo-EM structure of SKM-70S ribosomal stalled complex in the rot...
+Supramolecule #1: Cryo-EM structure of SKM-70S ribosomal stalled complex in the rot...
+Macromolecule #1: Large ribosomal subunit protein bL36A
+Macromolecule #2: Small ribosomal subunit protein uS12
+Macromolecule #3: Large ribosomal subunit protein uL3
+Macromolecule #5: Large ribosomal subunit protein bL31A
+Macromolecule #7: Large ribosomal subunit protein bL33
+Macromolecule #8: Large ribosomal subunit protein bL34
+Macromolecule #9: Large ribosomal subunit protein bL35
+Macromolecule #10: Small ribosomal subunit protein uS2
+Macromolecule #11: Small ribosomal subunit protein uS4
+Macromolecule #12: Small ribosomal subunit protein uS5
+Macromolecule #13: Small ribosomal subunit protein bS6, fully modified isoform
+Macromolecule #14: Small ribosomal subunit protein uS8
+Macromolecule #15: Small ribosomal subunit protein uS9
+Macromolecule #16: Small ribosomal subunit protein uS13
+Macromolecule #17: Small ribosomal subunit protein uS14
+Macromolecule #18: Small ribosomal subunit protein uS15
+Macromolecule #19: Small ribosomal subunit protein bS16
+Macromolecule #20: Small ribosomal subunit protein uS17
+Macromolecule #21: Small ribosomal subunit protein bS18
+Macromolecule #22: Small ribosomal subunit protein uS19
+Macromolecule #23: Small ribosomal subunit protein bS20
+Macromolecule #26: Large ribosomal subunit protein uL2
+Macromolecule #27: Large ribosomal subunit protein uL5
+Macromolecule #28: Large ribosomal subunit protein uL13
+Macromolecule #29: Large ribosomal subunit protein uL14
+Macromolecule #30: Large ribosomal subunit protein bL17
+Macromolecule #31: Large ribosomal subunit protein uL18
+Macromolecule #32: Large ribosomal subunit protein bL19
+Macromolecule #33: Large ribosomal subunit protein bL20
+Macromolecule #34: Large ribosomal subunit protein bL21
+Macromolecule #35: Large ribosomal subunit protein uL22
+Macromolecule #36: Large ribosomal subunit protein uL23
+Macromolecule #37: Large ribosomal subunit protein bL27
+Macromolecule #38: Large ribosomal subunit protein bL28
+Macromolecule #39: Large ribosomal subunit protein uL29
+Macromolecule #40: Large ribosomal subunit protein uL30
+Macromolecule #41: Large ribosomal subunit protein bL32
+Macromolecule #42: Large ribosomal subunit protein uL4
+Macromolecule #43: Large ribosomal subunit protein uL6
+Macromolecule #44: Large ribosomal subunit protein bL9
+Macromolecule #45: Large ribosomal subunit protein uL15
+Macromolecule #46: Large ribosomal subunit protein bL25
+Macromolecule #47: Small ribosomal subunit protein uS3
+Macromolecule #48: Small ribosomal subunit protein uS7
+Macromolecule #49: Small ribosomal subunit protein uS10
+Macromolecule #50: Small ribosomal subunit protein bS21
+Macromolecule #53: Large ribosomal subunit protein uL16
+Macromolecule #54: Small ribosomal subunit protein uS11
+Macromolecule #4: 23S rRNA
+Macromolecule #6: 16S rRNA
+Macromolecule #24: ermBL mRNA transcript
+Macromolecule #25: 5S rRNA
+Macromolecule #51: A/P-tRNA-Leu
+Macromolecule #52: P/E-tRNA-fMet
+Macromolecule #55: ZINC ION
+Macromolecule #56: MAGNESIUM ION
+Macromolecule #57: [(2~{S},3~{S},4~{R},5~{R},6~{S})-4-[(2~{S},3~{R},4~{S},5~{R},6~{S...
+Macromolecule #58: water
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.14 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 0.5 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Authors
United States,
Canada,
Germany, 4 items
Citation








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Processing
FIELD EMISSION GUN
