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- EMDB-33293: Cryo-EM structure of Cytochrome bo3 from Escherichia coli, apo st... -
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Open data
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Basic information
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Title | Cryo-EM structure of Cytochrome bo3 from Escherichia coli, apo structure with DMSO | |||||||||
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![]() | respiratory enzyme / membrane protein / heme protein / apo structure / OXIDOREDUCTASE | |||||||||
Function / homology | ![]() cytochrome o ubiquinol oxidase complex / oxidoreduction-driven active transmembrane transporter activity / ubiquinol oxidase (H+-transporting) / cytochrome bo3 ubiquinol oxidase activity / aerobic electron transport chain / oxidoreductase activity, acting on diphenols and related substances as donors, oxygen as acceptor / cytochrome-c oxidase activity / proton transmembrane transporter activity / ubiquinone binding / electron transport coupled proton transport ...cytochrome o ubiquinol oxidase complex / oxidoreduction-driven active transmembrane transporter activity / ubiquinol oxidase (H+-transporting) / cytochrome bo3 ubiquinol oxidase activity / aerobic electron transport chain / oxidoreductase activity, acting on diphenols and related substances as donors, oxygen as acceptor / cytochrome-c oxidase activity / proton transmembrane transporter activity / ubiquinone binding / electron transport coupled proton transport / : / ATP synthesis coupled electron transport / aerobic respiration / respiratory electron transport chain / electron transfer activity / copper ion binding / heme binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.09 Å | |||||||||
![]() | Nishida Y / Shigematsu H / Iwamoto T / Takashima S / Shintani Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases. Authors: Yuya Nishida / Sachiko Yanagisawa / Rikuri Morita / Hideki Shigematsu / Kyoko Shinzawa-Itoh / Hitomi Yuki / Satoshi Ogasawara / Ken Shimuta / Takashi Iwamoto / Chisa Nakabayashi / Waka ...Authors: Yuya Nishida / Sachiko Yanagisawa / Rikuri Morita / Hideki Shigematsu / Kyoko Shinzawa-Itoh / Hitomi Yuki / Satoshi Ogasawara / Ken Shimuta / Takashi Iwamoto / Chisa Nakabayashi / Waka Matsumura / Hisakazu Kato / Chai Gopalasingam / Takemasa Nagao / Tasneem Qaqorh / Yusuke Takahashi / Satoru Yamazaki / Katsumasa Kamiya / Ryuhei Harada / Nobuhiro Mizuno / Hideyuki Takahashi / Yukihiro Akeda / Makoto Ohnishi / Yoshikazu Ishii / Takashi Kumasaka / Takeshi Murata / Kazumasa Muramoto / Takehiko Tosha / Yoshitsugu Shiro / Teruki Honma / Yasuteru Shigeta / Minoru Kubo / Seiji Takashima / Yasunori Shintani / ![]() Abstract: Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to ...Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to rise and would become untreatable. The development of antibiotics with a different mechanism of action is seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), the essential respiratory enzymes for life. The steric conformation around the binding pocket of HCOs is highly conserved among bacteria and eukaryotes, yet the latter has an extra helix. This structural difference in the conserved allostery enabled us to rationally identify bacterial HCO-specific inhibitors: an antibiotic compound against ceftriaxone-resistant Neisseria gonorrhoeae. Molecular dynamics combined with resonance Raman spectroscopy and stopped-flow spectroscopy revealed an allosteric obstruction in the substrate accessing channel as a mechanism of inhibition. Our approach opens fresh avenues in modulating protein functions and broadens our options to overcome AMR. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 80.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.9 KB 23.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.6 KB | Display | ![]() |
Images | ![]() | 91.5 KB | ||
Masks | ![]() | 103 MB | ![]() | |
Filedesc metadata | ![]() | 8.7 KB | ||
Others | ![]() ![]() | 80.8 MB 80.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xmcMC ![]() 7xmaC ![]() 7xmbC ![]() 7xmdC 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: 1.18533 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #2
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Projections & Slices |
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
+Entire : Cytochrome bo3 ubiquinol oxidase
+Supramolecule #1: Cytochrome bo3 ubiquinol oxidase
+Macromolecule #1: Cytochrome bo(3) ubiquinol oxidase subunit 1
+Macromolecule #2: Ubiquinol oxidase subunit 2
+Macromolecule #3: Cytochrome bo(3) ubiquinol oxidase subunit 3
+Macromolecule #4: Cytochrome bo(3) ubiquinol oxidase subunit 4
+Macromolecule #5: HEME O
+Macromolecule #6: PROTOPORPHYRIN IX CONTAINING FE
+Macromolecule #7: COPPER (II) ION
+Macromolecule #8: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
+Macromolecule #9: UNKNOWN ATOM OR 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 | 13 mg/mL | |||||||||||||||
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Buffer | pH: 7.2 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 10 sec. / Pretreatment - Pressure: 0.007 kPa | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 12388 / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
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Image processing
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | ![]() PDB-7xmc: |