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Yorodumi- PDB-8cvm: Cutibacterium acnes 50S ribosomal subunit with P-site tRNA and Sa... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8cvm | ||||||
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Title | Cutibacterium acnes 50S ribosomal subunit with P-site tRNA and Sarecycline bound in the local refined map | ||||||
Components |
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Keywords | ANTIBIOTIC / ribosome / sarecycline / acne | ||||||
Function / homology | Function and homology information large ribosomal subunit / transferase activity / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / rRNA binding / negative regulation of translation / ribosome ...large ribosomal subunit / transferase activity / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / mRNA binding / metal ion binding / cytoplasm Similarity search - Function | ||||||
Biological species | Cutibacterium acnes (bacteria) Escherichia coli (E. coli) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.66 Å | ||||||
Authors | Lomakin, I.B. / Devarkar, S.C. / Bunick, C.G. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nucleic Acids Res / Year: 2023 Title: Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism. Authors: Ivan B Lomakin / Swapnil C Devarkar / Shivali Patel / Ayman Grada / Christopher G Bunick / Abstract: Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, ...Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, Cutibacterium acnes is implicated in acne pathogenesis and is, therefore, a main target for antibiotic-based acne therapy. We determined a 2.8-Å resolution structure of the 70S ribosome of Cutibacterium acnes by cryogenic electron microscopy and discovered that sarecycline, a narrow-spectrum antibiotic against Cutibacterium acnes, may inhibit two active sites of this bacterium's ribosome in contrast to the one site detected previously on the model ribosome of Thermus thermophilus. Apart from the canonical binding site at the mRNA decoding center, the second binding site for sarecycline exists at the nascent peptide exit tunnel, reminiscent of the macrolides class of antibiotics. The structure also revealed Cutibacterium acnes-specific features of the ribosomal RNA and proteins. Unlike the ribosome of the Gram-negative bacterium Escherichia coli, Cutibacterium acnes ribosome has two additional proteins, bS22 and bL37, which are also present in the ribosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We show that bS22 and bL37 have antimicrobial properties and may be involved in maintaining the healthy homeostasis of the human skin microbiome. #1: Journal: To Be Published Title: The structure of the Cutibacterium acnes 70S ribosome Authors: Lomakin, I.B. / Devarkar, S.C. / Grada, A. / Bunick, C.G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8cvm.cif.gz | 2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8cvm.ent.gz | 1.6 MB | Display | PDB format |
PDBx/mmJSON format | 8cvm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8cvm_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 8cvm_full_validation.pdf.gz | 1.9 MB | Display | |
Data in XML | 8cvm_validation.xml.gz | 138.7 KB | Display | |
Data in CIF | 8cvm_validation.cif.gz | 243.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cv/8cvm ftp://data.pdbj.org/pub/pdb/validation_reports/cv/8cvm | HTTPS FTP |
-Related structure data
Related structure data | 27009MC 8crxC 8cvoC 8cwoC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
+50S ribosomal protein ... , 29 types, 29 molecules cdefgijklmnopqrstuvwxyz0124V3
-RNA chain , 3 types, 3 molecules abC
#28: RNA chain | Mass: 1002554.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Cutibacterium acnes (bacteria) |
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#29: RNA chain | Mass: 38770.055 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Cutibacterium acnes (bacteria) / References: GenBank: 2179609306 |
#31: RNA chain | Mass: 24846.902 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (E. coli) / References: GenBank: 732678099 |
-Non-polymers , 4 types, 435 molecules
#33: Chemical | ChemComp-MG / #34: Chemical | ChemComp-ZN / #35: Chemical | ChemComp-V7A / | #36: Water | ChemComp-HOH / | |
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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: 50S subunit from 70S ribosome with mRNA, P-site tRNA and Sarecycline bound Type: RIBOSOME / Entity ID: #1-#32 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Cutibacterium acnes (bacteria) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % |
-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 / Nominal defocus max: 2000 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 2.1 sec. / Electron dose: 30.56 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1108852 | ||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.66 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 70853 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL |