+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-23667 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | A. baumannii Ribosome-Eravacycline complex: 50S | |||||||||
![]() | density modified map of the Acinetobacter baumannii 50S-Era complex | |||||||||
![]() |
| |||||||||
![]() | Acinetobacter baumannii / ribosome / eravacycline / antibiotic | |||||||||
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 / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.54 Å | |||||||||
![]() | Morgan CE / Yu EW | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 76.1 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 41 KB 41 KB | Display Display | ![]() |
Images | ![]() | 102.5 KB | ||
Filedesc metadata | ![]() | 9.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7m4vMC ![]() 7m4pC ![]() 7m4qC ![]() 7m4uC ![]() 7m4wC ![]() 7m4xC ![]() 7m4yC ![]() 7m4zC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | density modified map of the Acinetobacter baumannii 50S-Era complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.848 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
+Entire : Acinetobacter baumannii 50S-Eravacycline complex
+Supramolecule #1: Acinetobacter baumannii 50S-Eravacycline complex
+Macromolecule #1: 50S ribosomal protein L33
+Macromolecule #2: 50S ribosomal protein L34
+Macromolecule #3: 50S ribosomal protein L35
+Macromolecule #4: 50S ribosomal protein L36
+Macromolecule #7: 50S ribosomal protein L2
+Macromolecule #8: 50S ribosomal protein L3
+Macromolecule #9: 50S ribosomal protein L4
+Macromolecule #10: 50S ribosomal protein L5
+Macromolecule #11: 50S ribosomal protein L6
+Macromolecule #12: 50S ribosomal protein L9
+Macromolecule #13: 50S ribosomal protein L13
+Macromolecule #14: 50S ribosomal protein L14
+Macromolecule #15: 50S ribosomal protein L15
+Macromolecule #16: 50S ribosomal protein L16
+Macromolecule #17: 50S ribosomal protein L17
+Macromolecule #18: 50S ribosomal protein L18
+Macromolecule #19: 50S ribosomal protein L19
+Macromolecule #20: 50S ribosomal protein L20
+Macromolecule #21: 50S ribosomal protein L21
+Macromolecule #22: 50S ribosomal protein L22
+Macromolecule #23: 50S ribosomal protein L23
+Macromolecule #24: 50S ribosomal protein L24
+Macromolecule #25: 50S ribosomal protein L25
+Macromolecule #26: 50S ribosomal protein L27
+Macromolecule #27: 50S ribosomal protein L28
+Macromolecule #28: 50S ribosomal protein L29
+Macromolecule #29: 50S ribosomal protein L30
+Macromolecule #30: 50S ribosomal protein L32
+Macromolecule #5: 23s ribosomal RNA
+Macromolecule #6: 5s ribosomal RNA
+Macromolecule #31: ZINC ION
+Macromolecule #32: Eravacycline
+Macromolecule #33: MAGNESIUM ION
+Macromolecule #34: water
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.6 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 46.0 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 |
-
Image processing
Startup model | Type of model: INSILICO MODEL / In silico model: ab initio |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.54 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 92112 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC |