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Open data
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Basic information
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Title | E.coli gyrase holocomplex with 217 bp DNA and Albi-1 (site TG) | |||||||||
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![]() | type II topoisomerase / antibiotic / albicidin / DNA gyrase / ISOMERASE | |||||||||
Function / homology | ![]() negative regulation of DNA-templated DNA replication / DNA negative supercoiling activity / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity / DNA topoisomerase (ATP-hydrolysing) / DNA topological change / ATP-dependent activity, acting on DNA / DNA-templated DNA replication / chromosome / response to xenobiotic stimulus ...negative regulation of DNA-templated DNA replication / DNA negative supercoiling activity / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity / DNA topoisomerase (ATP-hydrolysing) / DNA topological change / ATP-dependent activity, acting on DNA / DNA-templated DNA replication / chromosome / response to xenobiotic stimulus / response to antibiotic / DNA-templated transcription / DNA binding / ATP binding / identical protein binding / membrane / metal ion binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.25 Å | |||||||||
![]() | Ghilarov D / Heddle JGH | |||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Molecular mechanism of topoisomerase poisoning by the peptide antibiotic albicidin. Authors: Elizabeth Michalczyk / Kay Hommernick / Iraj Behroz / Marcel Kulike / Zuzanna Pakosz-Stępień / Lukasz Mazurek / Maria Seidel / Maria Kunert / Karine Santos / Holger von Moeller / Bernhard ...Authors: Elizabeth Michalczyk / Kay Hommernick / Iraj Behroz / Marcel Kulike / Zuzanna Pakosz-Stępień / Lukasz Mazurek / Maria Seidel / Maria Kunert / Karine Santos / Holger von Moeller / Bernhard Loll / John B Weston / Andi Mainz / Jonathan G Heddle / Roderich D Süssmuth / Dmitry Ghilarov / ![]() ![]() ![]() Abstract: The peptide antibiotic albicidin is a DNA topoisomerase inhibitor with low-nanomolar bactericidal activity towards fluoroquinolone-resistant Gram-negative pathogens. However, its mode of action is ...The peptide antibiotic albicidin is a DNA topoisomerase inhibitor with low-nanomolar bactericidal activity towards fluoroquinolone-resistant Gram-negative pathogens. However, its mode of action is poorly understood. We determined a 2.6 Å resolution cryoelectron microscopy structure of a ternary complex between topoisomerase DNA gyrase, a 217 bp double-stranded DNA fragment and albicidin. Albicidin employs a dual binding mechanism where one end of the molecule obstructs the crucial gyrase dimer interface, while the other intercalates between the fragments of cleaved DNA substrate. Thus, albicidin efficiently locks DNA gyrase, preventing it from religating DNA and completing its catalytic cycle. Two additional structures of this trapped state were determined using synthetic albicidin analogues that demonstrate improved solubility, and activity against a range of gyrase variants and topoisomerase IV. The extraordinary promiscuity of the DNA-intercalating region of albicidins and their excellent performance against fluoroquinolone-resistant bacteria holds great promise for the development of last-resort antibiotics. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
Map data | ![]() | 230.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.9 KB 22.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.2 KB | Display | ![]() |
Images | ![]() | 55.3 KB | ||
Others | ![]() ![]() | 226.3 MB 226.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7z9kMC ![]() 7z9cC ![]() 7z9gC ![]() 7z9mC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_14573_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_14573_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : Escherichia coli gyrase holocomplex with 217 bp phage Mu SGS DNA ...
+Supramolecule #1: Escherichia coli gyrase holocomplex with 217 bp phage Mu SGS DNA ...
+Supramolecule #2: Escherichia coli gyrase holocomplex
+Supramolecule #3: 217 bp phage Mu SGS DNA
+Macromolecule #1: DNA gyrase subunit A
+Macromolecule #2: DNA gyrase subunit B
+Macromolecule #3: DNA (5'-D(P*AP*AP*AP*TP*CP*TP*GP*TP*GP*CP*GP*GP*GP*T)-3')
+Macromolecule #4: DNA (5'-D(P*AP*GP*AP*AP*TP*CP*AP*GP*GP*CP*AP*TP*AP*A)-3')
+Macromolecule #5: DNA (5'-D(*AP*AP*TP*CP*AP*CP*CP*CP*GP*CP*AP*CP*AP*GP*AP*TP*TP*T)-3')
+Macromolecule #6: DNA (5'-D(*GP*AP*TP*TP*TP*TP*AP*TP*GP*CP*CP*TP*GP*AP*TP*TP*CP*T)-3')
+Macromolecule #7: 4-[[4-[[5-[[(2S)-2-[[5-[(4-cyanophenyl)carbonylamino]pyridin-2-yl...
+Macromolecule #8: MAGNESIUM ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 12 mg/mL |
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Buffer | pH: 8 / Component - Concentration: 20.0 mM / Component - Name: HEPES |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.9 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |