+Open data
-Basic information
Entry | Database: PDB / ID: 5tcu | |||||||||
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Title | Methicillin sensitive Staphylococcus aureus 70S ribosome | |||||||||
Components |
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Keywords | ribosome/antibiotic / 70S ribosome / cryoEM / ribosome / Staphylococcus aureus / ribosome-antibiotic complex | |||||||||
Function / homology | Function and homology information 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 ...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 / tRNA binding / cytoplasmic translation / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / RNA binding / zinc ion binding / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Staphylococcus aureus (bacteria) Staphylococcus aureus subsp. aureus NCTC 8325 (bacteria) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Eyal, Z. / Ahmed, T. / Belousoff, N. / Mishra, S. / Matzov, D. / Bashan, A. / Zimmerman, E. / Lithgow, T. / Bhushan, S. / Yonath, A. | |||||||||
Funding support | Australia, European Union, 2items
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Citation | Journal: mBio / Year: 2017 Title: Structural Basis for Linezolid Binding Site Rearrangement in the Ribosome. Authors: Matthew J Belousoff / Zohar Eyal / Mazdak Radjainia / Tofayel Ahmed / Rebecca S Bamert / Donna Matzov / Anat Bashan / Ella Zimmerman / Satabdi Mishra / David Cameron / Hans Elmlund / Anton Y ...Authors: Matthew J Belousoff / Zohar Eyal / Mazdak Radjainia / Tofayel Ahmed / Rebecca S Bamert / Donna Matzov / Anat Bashan / Ella Zimmerman / Satabdi Mishra / David Cameron / Hans Elmlund / Anton Y Peleg / Shashi Bhushan / Trevor Lithgow / Ada Yonath / Abstract: An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in the 70S ribosomes from a clinical isolate of This high-resolution ...An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in the 70S ribosomes from a clinical isolate of This high-resolution structural information demonstrated that a single amino acid deletion in ribosomal protein uL3 confers linezolid resistance despite being located 24 Å away from the linezolid binding pocket in the peptidyl-transferase center. The mutation induces a cascade of allosteric structural rearrangements of the rRNA that ultimately results in the alteration of the antibiotic binding site. The growing burden on human health caused by various antibiotic resistance mutations now includes prevalent resistance to last-line antimicrobial drugs such as linezolid and daptomycin. Structure-informed drug modification represents a frontier with respect to designing advanced clinical therapies, but success in this strategy requires rapid, facile means to shed light on the structural basis for drug resistance (D. Brown, Nat Rev Drug Discov 14:821-832, 2015, https://doi.org/10.1038/nrd4675). Here, detailed structural information demonstrates that a common mechanism is at play in linezolid resistance and provides a step toward the redesign of oxazolidinone antibiotics, a strategy that could thwart known mechanisms of linezolid resistance. | |||||||||
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 | 5tcu.cif.gz | 2.9 MB | Display | PDBx/mmCIF format |
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PDB format | pdb5tcu.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 5tcu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5tcu_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 5tcu_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 5tcu_validation.xml.gz | 224.3 KB | Display | |
Data in CIF | 5tcu_validation.cif.gz | 372.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tc/5tcu ftp://data.pdbj.org/pub/pdb/validation_reports/tc/5tcu | HTTPS FTP |
-Related structure data
Related structure data | 8402MC 8369C 5t7vC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 6 types, 6 molecules AXEDBC
#1: RNA chain | Mass: 502935.844 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: GenBank: 87201381 |
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#20: RNA chain | Mass: 4157.573 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: ? Source: (synth.) Staphylococcus aureus subsp. aureus NCTC 8325 (bacteria) |
#21: RNA chain | Mass: 24156.334 Da / Num. of mol.: 1 / Source method: obtained synthetically Source: (synth.) Staphylococcus aureus subsp. aureus NCTC 8325 (bacteria) References: GenBank: 1061489863 |
#22: RNA chain | Mass: 24485.539 Da / Num. of mol.: 1 / Source method: obtained synthetically Source: (synth.) Staphylococcus aureus subsp. aureus NCTC 8325 (bacteria) References: GenBank: 1061489863 |
#23: RNA chain | Mass: 946687.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: GenBank: 87201381 |
#24: RNA chain | Mass: 36692.801 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: GenBank: 87201381 |
-30S ribosomal protein ... , 18 types, 18 molecules SBSCSDSESGSFSHS1S2S3S4S5S6S7S8S9SISA
#2: Protein | Mass: 22684.201 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW12 |
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#3: Protein | Mass: 22849.145 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FXK6 |
#4: Protein | Mass: 16522.119 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW23 |
#5: Protein | Mass: 11239.766 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2G113 |
#6: Protein | Mass: 17695.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: P48940 |
#7: Protein | Mass: 14622.014 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW20 |
#8: Protein | Mass: 14312.321 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW39 |
#9: Protein | Mass: 9243.610 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2YYP5 |
#10: Protein | Mass: 12047.609 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW31 |
#11: Protein | Mass: 15189.673 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: P0A0H0 |
#12: Protein | Mass: 12843.768 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW30 |
#13: Protein | Mass: 7186.573 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW19 |
#14: Protein | Mass: 10503.135 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2G2Q1 |
#15: Protein | Mass: 9291.743 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FZ45 |
#16: Protein | Mass: 9366.860 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW15 |
#17: Protein | Mass: 6574.833 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2G111 |
#18: Protein | Mass: 9010.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FW10 |
#19: Protein | Mass: 8609.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Staphylococcus aureus (strain NCTC 8325) (bacteria) Strain: NCTC 8325 / References: UniProt: Q2FXY6 |
+50S ribosomal protein ... , 28 types, 28 molecules L2LCLJLKLLLMLNLOLPLQLRL1L3L4L5L6L7L8L9LALBLDLELSLGLHLILF
-Non-polymers , 2 types, 130 molecules
#53: Chemical | ChemComp-PAR / |
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#54: Chemical | ChemComp-MG / |
-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: Methicillin sensitive Staphylococcus aureus 70S ribosome (ATCC 35556) Type: RIBOSOME / Entity ID: #1-#52 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Staphylococcus aureus (bacteria) |
Buffer solution | pH: 7.6 |
Specimen | Conc.: 0.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/2 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: (dev_2429: phenix.real_space_refine) / Classification: refinement |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 126000 / Symmetry type: POINT |
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL |