6DDG

Structure of the 50S ribosomal subunit from Methicillin Resistant Staphylococcus aureus in complex with the oxazolidinone antibiotic LZD-6

Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history. 


Literature

cryoEM-Guided Development of Antibiotics for Drug-Resistant Bacteria.

Belousoff, M.J., Venugopal, H., Wright, A., Seoner, S., Stuart, I., Stubenrauch, C., Bamert, R.S., Lupton, D.W., Lithgow, T.

(2019) ChemMedChem 14: 527-531

  • DOI: https://doi.org/10.1002/cmdc.201900042
  • Primary Citation of Related Structures:  
    6DDD, 6DDG

  • PubMed 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 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.

    • Organizational Affiliation: 

    Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, 3800, Australia.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L19116Staphylococcus aureusMutation(s): 0 
UniProt
Find proteins for Q2FZ42 (Staphylococcus aureus (strain NCTC 8325 / PS 47))
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L2276Staphylococcus aureusMutation(s): 0 
UniProt
Find proteins for P60430 (Staphylococcus aureus (strain NCTC 8325 / PS 47))
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L20118Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L21102Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L22116Staphylococcus aureusMutation(s): 0 
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L2391Staphylococcus aureusMutation(s): 0 
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L24105Staphylococcus aureusMutation(s): 0 
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L25217Staphylococcus aureusMutation(s): 0 
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L2785Staphylococcus aureusMutation(s): 0 
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L2862Staphylococcus aureusMutation(s): 0 
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Entity ID: 11
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L2969Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 12
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3217Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 13
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3059Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 14
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3257Staphylococcus aureusMutation(s): 0 
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Entity ID: 15
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3349Staphylococcus aureusMutation(s): 0 
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Entity ID: 16
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3445Staphylococcus aureusMutation(s): 0 
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Entity ID: 17
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3565Staphylococcus aureusMutation(s): 0 
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Entity ID: 18
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L3637Staphylococcus aureusMutation(s): 0 
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Entity ID: 19
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L4207Staphylococcus aureusMutation(s): 0 
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Entity ID: 20
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L13T [auth V]145Staphylococcus aureusMutation(s): 0 
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Find proteins for Q2FW38 (Staphylococcus aureus (strain NCTC 8325 / PS 47))
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Entity ID: 21
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L14U [auth W]122Staphylococcus aureusMutation(s): 0 
UniProt
Find proteins for Q2FW16 (Staphylococcus aureus (strain NCTC 8325 / PS 47))
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Entity ID: 22
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L15V [auth X]146Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 23
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L16W [auth Y]144Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 24
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L17X [auth Z]122Staphylococcus aureusMutation(s): 0 
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Entity ID: 25
MoleculeChains Sequence LengthOrganismDetailsImage
50S ribosomal protein L18Y [auth a]119Staphylococcus aureusMutation(s): 0 
UniProt
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Entity ID: 26
MoleculeChains LengthOrganismImage
23S rRNAZ [auth 1]2,923Staphylococcus aureus
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Entity ID: 27
MoleculeChains LengthOrganismImage
5S rRNAAA [auth 2]115Staphylococcus aureus
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Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
G6M
Query on G6M
Download Ideal Coordinates CCD File 
BA [auth 1]2-chloro-N-({(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide
C16 H19 Cl F N3 O4
BLEAWUVPPDXJFJ-LBPRGKRZSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)AustraliaProgram Grant 1092262

Revision History  (Full details and data files)

  • Version 1.0: 2019-03-20
    Type: Initial release
  • Version 1.1: 2019-12-18
    Changes: Author supporting evidence, Other