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Open data
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Basic information
Entry | Database: PDB / ID: 7m4u | ||||||
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Title | A. baumannii Ribosome-Eravacycline complex: 30S | ||||||
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![]() | RIBOSOME / Acinetobacter baumannii / eravacycline / antibiotic | ||||||
Function / homology | ![]() ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex ...ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / RNA binding / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.71 Å | ||||||
![]() | Morgan, C.E. / Yu, E.W. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM Determination of Eravacycline-Bound Structures of the Ribosome and the Multidrug Efflux Pump AdeJ of Acinetobacter baumannii. Authors: Zhemin Zhang / Christopher E Morgan / Robert A Bonomo / Edward W Yu / ![]() Abstract: Antibiotic-resistant strains of the Gram-negative pathogen Acinetobacter baumannii have emerged as a significant global health threat. One successful therapeutic option to treat bacterial infections ...Antibiotic-resistant strains of the Gram-negative pathogen Acinetobacter baumannii have emerged as a significant global health threat. One successful therapeutic option to treat bacterial infections has been to target the bacterial ribosome. However, in many cases, multidrug efflux pumps within the bacterium recognize and extrude these clinically important antibiotics designed to inhibit the protein synthesis function of the bacterial ribosome. Thus, multidrug efflux within A. baumannii and other highly drug-resistant strains is a major cause of failure of drug-based treatments of infectious diseases. We here report the first structures of the cinetobacter rug fflux (Ade)J pump in the presence of the antibiotic eravacycline, using single-particle cryo-electron microscopy (cryo-EM). We also describe cryo-EM structures of the eravacycline-bound forms of the A. baumannii ribosome, including the 70S, 50S, and 30S forms. Our data indicate that the AdeJ pump primarily uses hydrophobic interactions to bind eravacycline, while the 70S ribosome utilizes electrostatic interactions to bind this drug. Our work here highlights how an antibiotic can bind multiple bacterial targets through different mechanisms and potentially enables drug optimization by taking advantage of these different modes of ligand binding. Acinetobacter baumannii has developed into a highly antibiotic-resistant Gram-negative pathogen. The prevalent AdeJ multidrug efflux pump mediates resistance to different classes of antibiotics known to inhibit the function of the 70S ribosome. Here, we report the first structures of the A. baumannii AdeJ pump, both in the absence and presence of eravacycline. We also describe structures of the A. baumannii ribosome bound by this antibiotic. Our results indicate that AdeJ and the ribosome use very distinct binding modes for drug recognition. Our work will ultimately enable structure-based drug discovery to combat antibiotic-resistant A. baumannii infection. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.2 MB | Display | ![]() |
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PDB format | ![]() | 906.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 23666MC ![]() 7m4pC ![]() 7m4qC ![]() 7m4vC ![]() 7m4wC ![]() 7m4xC ![]() 7m4yC ![]() 7m4zC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-RNA chain , 1 types, 1 molecules a
#1: RNA chain | Mass: 500297.531 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: GenBank: 1211343212 |
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-30S ribosomal protein ... , 20 types, 20 molecules bcdefghijklmnopqrstu
#2: Protein | Mass: 27680.357 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: V5VBC2 |
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#3: Protein | Mass: 27972.461 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: V5V9N0 |
#4: Protein | Mass: 23311.818 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IA15 |
#5: Protein | Mass: 17181.766 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IA22 |
#6: Protein | Mass: 14986.952 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IBC1 |
#7: Protein | Mass: 17733.699 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7I7S0 |
#8: Protein | Mass: 14250.667 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IA25 |
#9: Protein | Mass: 14287.610 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: V5VBA5 |
#10: Protein | Mass: 11718.531 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: A0A009L7S8 |
#11: Protein | Mass: 13558.512 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: A0A4R0F9S8 |
#12: Protein | Mass: 13797.134 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7I7R9 |
#13: Protein | Mass: 13295.635 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IA17 |
#14: Protein | Mass: 11438.427 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IA26 |
#15: Protein | Mass: 10145.600 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7I3U0 |
#16: Protein | Mass: 11223.060 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: A0A1V3DIZ9 |
#17: Protein | Mass: 9543.101 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IA30 |
#18: Protein | Mass: 9009.452 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: A0A022IPE7 |
#19: Protein | Mass: 10206.957 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7IA35 |
#20: Protein | Mass: 9723.420 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: B7I5N9 |
#21: Protein | Mass: 8474.033 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: A0A0Q7FMS9 |
-Non-polymers , 3 types, 275 molecules ![](data/chem/img/YQM.gif)
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![](data/chem/img/HOH.gif)
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#22: Chemical | ChemComp-YQM / | ||
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#23: Chemical | ChemComp-MG / #24: Water | ChemComp-HOH / | |
-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 |
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Sample preparation
Component | Name: A baumannii 30S ribosome in complex with Eravacycline / Type: RIBOSOME / Entity ID: #1-#21 / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.6 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 46 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19_4080: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: cryoSPARC / Category: final Euler assignment | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.71 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 47367 Details: Resolution of 30S core = 2.80. Resolution of 30S head = 2.71. Symmetry type: POINT | ||||||||||||||||||||||||
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