+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25100 | |||||||||
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Title | Unmethylated Mtb Ribosome 50S with SEQ-9 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | unmethylated / Mtb ribosome / drug discovery / SEQ-9 / Structural Genomics / TB Structural Genomics Consortium / TBSGC / RIBOSOME-ANTIBIOTIC complex | |||||||||
Function / homology | Function and homology information large ribosomal subunit / small ribosomal subunit / 5S rRNA binding / transferase activity / ribosomal large subunit assembly / cytosolic large ribosomal subunit / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome ...large ribosomal subunit / small ribosomal subunit / 5S rRNA binding / transferase activity / ribosomal large subunit assembly / cytosolic large ribosomal subunit / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / zinc ion binding / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | Mycobacterium tuberculosis (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
Authors | Xing Z / Cui Z | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell / Year: 2023 Title: Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents. Authors: Jidong Zhang / Christine Lair / Christine Roubert / Kwame Amaning / María Belén Barrio / Yannick Benedetti / Zhicheng Cui / Zhongliang Xing / Xiaojun Li / Scott G Franzblau / Nicolas ...Authors: Jidong Zhang / Christine Lair / Christine Roubert / Kwame Amaning / María Belén Barrio / Yannick Benedetti / Zhicheng Cui / Zhongliang Xing / Xiaojun Li / Scott G Franzblau / Nicolas Baurin / Florence Bordon-Pallier / Cathy Cantalloube / Stephanie Sans / Sandra Silve / Isabelle Blanc / Laurent Fraisse / Alexey Rak / Lasse B Jenner / Gulnara Yusupova / Marat Yusupov / Junjie Zhang / Takushi Kaneko / T J Yang / Nader Fotouhi / Eric Nuermberger / Sandeep Tyagi / Fabrice Betoudji / Anna Upton / James C Sacchettini / Sophie Lagrange / Abstract: The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding ...The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classic macrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb. Structures of the ribosome with bound inhibitors were used to optimize sequanamycin to produce the advanced lead compound SEQ-9. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and it demonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results support further investigation of this series as TB clinical candidates, with the potential for use in new regimens against drug-susceptible and drug-resistant TB. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25100.map.gz | 140.9 MB | EMDB map data format | |
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Header (meta data) | emd-25100-v30.xml emd-25100.xml | 71.5 KB 71.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_25100_fsc.xml | 14.9 KB | Display | FSC data file |
Images | emd_25100.png | 50.6 KB | ||
Masks | emd_25100_msk_1.map | 282.6 MB | Mask map | |
Filedesc metadata | emd-25100.cif.gz | 14.3 KB | ||
Others | emd_25100_half_map_1.map.gz emd_25100_half_map_2.map.gz | 262 MB 262 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25100 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25100 | HTTPS FTP |
-Validation report
Summary document | emd_25100_validation.pdf.gz | 1020.2 KB | Display | EMDB validaton report |
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Full document | emd_25100_full_validation.pdf.gz | 1019.8 KB | Display | |
Data in XML | emd_25100_validation.xml.gz | 22.8 KB | Display | |
Data in CIF | emd_25100_validation.cif.gz | 30 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25100 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25100 | HTTPS FTP |
-Related structure data
Related structure data | 7sfrMC 7azoC 7azsC 7kgbC C: citing same article (ref.) M: atomic model generated by this map |
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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_25100.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_25100_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_25100_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_25100_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Unmethylated Mth Ribosome with SEQ-9
+Supramolecule #1: Unmethylated Mth Ribosome with SEQ-9
+Macromolecule #1: 50S ribosomal protein L32
+Macromolecule #2: 50S ribosomal protein L33
+Macromolecule #3: 50S ribosomal protein L34
+Macromolecule #4: 50S ribosomal protein L35
+Macromolecule #5: 50S ribosomal protein L36
+Macromolecule #6: 50S ribosomal protein L31
+Macromolecule #9: 50S ribosomal protein L2
+Macromolecule #10: 50S ribosomal protein L3
+Macromolecule #11: 50S ribosomal protein L4
+Macromolecule #12: 50S ribosomal protein L5
+Macromolecule #13: 50S ribosomal protein L6
+Macromolecule #14: 50S ribosomal protein L9
+Macromolecule #15: 50S ribosomal protein L13
+Macromolecule #16: 50S ribosomal protein L14
+Macromolecule #17: 50S ribosomal protein L15
+Macromolecule #18: 50S ribosomal protein L16
+Macromolecule #19: 50S ribosomal protein L17
+Macromolecule #20: 50S ribosomal protein L18
+Macromolecule #21: 50S ribosomal protein L19
+Macromolecule #22: 50S ribosomal protein L20
+Macromolecule #23: 50S ribosomal protein L21
+Macromolecule #24: 50S ribosomal protein L22
+Macromolecule #25: 50S ribosomal protein L23
+Macromolecule #26: 50S ribosomal protein L24
+Macromolecule #27: 50S ribosomal protein L25
+Macromolecule #28: 50S ribosomal protein L27
+Macromolecule #29: 50S ribosomal protein L28
+Macromolecule #30: 50S ribosomal protein L29
+Macromolecule #31: 50S ribosomal protein L30
+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 type Z
+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: peptide
+Macromolecule #7: 23S rRNA
+Macromolecule #8: 5S rRNA
+Macromolecule #32: 16S rRNA
+Macromolecule #52: ZINC ION
+Macromolecule #53: Sequanamycin 9
+Macromolecule #54: MAGNESIUM ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 4 sec. | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK III | |||||||||||||||
Details | Monodispersed unmethylated Mtb ribosome with SEQ-9 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 42.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |