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Yorodumi- PDB-7kgb: CryoEM structure of A2296-methylated Mycobacterium tuberculosis r... -
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-Basic information
Entry | Database: PDB / ID: 7kgb | ||||||
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Title | CryoEM structure of A2296-methylated Mycobacterium tuberculosis ribosome bound with SEQ-9 | ||||||
Components |
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Keywords | RIBOSOME/ANTIBIOTIC / Antibiotic / Methylation / Pathogen / ribosome / RIBOSOME-ANTIBIOTIC complex | ||||||
Function / homology | Function and homology information peptidoglycan-based cell wall / large ribosomal subunit / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / transferase activity / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit ...peptidoglycan-based cell wall / large ribosomal subunit / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / transferase activity / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / response to antibiotic / mRNA binding / RNA binding / zinc ion binding / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Mycobacterium tuberculosis (bacteria) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||
Authors | Cui, Z. / Zhang, J. | ||||||
Funding support | United States, 1items
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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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7kgb.cif.gz | 3.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7kgb.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7kgb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7kgb_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 7kgb_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 7kgb_validation.xml.gz | 202.6 KB | Display | |
Data in CIF | 7kgb_validation.cif.gz | 361.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kg/7kgb ftp://data.pdbj.org/pub/pdb/validation_reports/kg/7kgb | HTTPS FTP |
-Related structure data
Related structure data | 22865MC 7azoC 7azsC 7sfrC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
+50S ribosomal protein ... , 30 types, 30 molecules 012346CDEFGHJKLMNOPQRSTUVWXYZv
-RNA chain , 4 types, 4 molecules ABay
#7: RNA chain | Mass: 1017876.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: GenBank: 1251771536 |
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#8: RNA chain | Mass: 37097.238 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: GenBank: 1251771551 |
#32: RNA chain | Mass: 498415.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: GenBank: 1464449751 |
#52: RNA chain | Mass: 24802.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv |
-30S ribosomal protein ... , 18 types, 18 molecules cdefghijklmnopqrst
#33: Protein | Mass: 30071.018 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH37 |
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#34: Protein | Mass: 23515.898 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH35 |
#35: Protein | Mass: 22925.242 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH33 |
#36: Protein | Mass: 10952.728 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH31 |
#37: Protein | Mass: 17633.418 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH29 |
#38: Protein | Mass: 14432.563 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH27 |
#39: Protein | Mass: 16465.061 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH25 |
#40: Protein | Mass: 11452.340 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH67 |
#41: Protein | Mass: 14815.918 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH65 |
#42: Protein | Mass: 13882.341 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH63 |
#43: Protein | Mass: 14383.779 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH61 |
#44: Protein | Mass: 6841.249 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH57 |
#45: Protein | Mass: 10500.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH55 |
#46: Protein | Mass: 17466.100 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH53 |
#47: Protein | Mass: 14776.373 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH51 |
#48: Protein | Mass: 9565.279 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH49 |
#49: Protein | Mass: 10830.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH45 |
#50: Protein | Mass: 9428.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / References: UniProt: P9WH41 |
-Non-polymers , 3 types, 454 molecules
#53: Chemical | ChemComp-ZN / #54: Chemical | ChemComp-WDP / | #55: Chemical | ChemComp-MG / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: A2296-methylated Mycobacterium tuberculosis ribosome bound with SEQ-9 Type: RIBOSOME / Entity ID: #1-#52 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Mycobacterium tuberculosis H37Rv (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 mesh size: 300 divisions/in. / Grid type: Quantifoil R2/1 |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm |
Image recording | Electron dose: 48 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 6481 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1065544 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 63.5 Å2 | ||||||||||||||||||||||||
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