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- EMDB-7870: Structure of the 50S ribosomal subunit from Methicillin Resistant... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7870 | |||||||||
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Title | Structure of the 50S ribosomal subunit from Methicillin Resistant Staphylococcus aureus in complex with the oxazolidinone antibiotic LZD-6 | |||||||||
![]() | 50S ribosomal subunit from MRSA in complex with an oxazolidinone antibiotic: LZD-6 | |||||||||
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Function / homology | ![]() 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 / ribonucleoprotein complex / translation / mRNA binding / RNA binding / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Belousoff MJ / Venugopal H / Bamert RS / Lithgow T | |||||||||
Funding support | ![]()
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![]() | ![]() Title: cryoEM-Guided Development of Antibiotics for Drug-Resistant Bacteria. Authors: Matthew J Belousoff / Hari Venugopal / Alexander Wright / Samuel Seoner / Isabella Stuart / Chris Stubenrauch / Rebecca S Bamert / David W Lupton / Trevor Lithgow / ![]() Abstract: While the ribosome is a common target for antibiotics, challenges with crystallography can impede the development of new bioactives using structure-based drug design approaches. In this study we ...While the ribosome is a common target for antibiotics, challenges with crystallography can impede the development of new bioactives using structure-based drug design approaches. In this study we exploit common structural features present in linezolid-resistant forms of both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) to redesign the antibiotic. Enabled by rapid and facile cryoEM structures, this process has identified (S)-2,2-dichloro-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide (LZD-5) and (S)-2-chloro-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl) acetamide (LZD-6), which inhibit the ribosomal function and growth of linezolid-resistant MRSA and VRE. The strategy discussed highlights the potential for cryoEM to facilitate the development of novel bioactive materials. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 16.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 36.9 KB 36.9 KB | Display Display | ![]() |
Images | ![]() | 101.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6ddgMC ![]() 7867C ![]() 6dddC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | 50S ribosomal subunit from MRSA in complex with an oxazolidinone antibiotic: LZD-6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : 50S Ribosomal subunit from MRSA in complex with oxazolidinone LZD-5
+Supramolecule #1: 50S Ribosomal subunit from MRSA in complex with oxazolidinone LZD-5
+Macromolecule #1: 50S ribosomal protein L19
+Macromolecule #2: 50S ribosomal protein L2
+Macromolecule #3: 50S ribosomal protein L20
+Macromolecule #4: 50S ribosomal protein L21
+Macromolecule #5: 50S ribosomal protein L22
+Macromolecule #6: 50S ribosomal protein L23
+Macromolecule #7: 50S ribosomal protein L24
+Macromolecule #8: 50S ribosomal protein L25
+Macromolecule #9: 50S ribosomal protein L27
+Macromolecule #10: 50S ribosomal protein L28
+Macromolecule #11: 50S ribosomal protein L29
+Macromolecule #12: 50S ribosomal protein L3
+Macromolecule #13: 50S ribosomal protein L30
+Macromolecule #14: 50S ribosomal protein L32
+Macromolecule #15: 50S ribosomal protein L33
+Macromolecule #16: 50S ribosomal protein L34
+Macromolecule #17: 50S ribosomal protein L35
+Macromolecule #18: 50S ribosomal protein L36
+Macromolecule #19: 50S ribosomal protein L4
+Macromolecule #20: 50S ribosomal protein L13
+Macromolecule #21: 50S ribosomal protein L14
+Macromolecule #22: 50S ribosomal protein L15
+Macromolecule #23: 50S ribosomal protein L16
+Macromolecule #24: 50S ribosomal protein L17
+Macromolecule #25: 50S ribosomal protein L18
+Macromolecule #26: 23S rRNA
+Macromolecule #27: 5S rRNA
+Macromolecule #28: 2-chloro-N-({(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.3 mg/mL | ||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R2/1 / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK III |
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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: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Number classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 49223 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |