[English] 日本語
![](img/lk-miru.gif)
- EMDB-28819: Structure of yeast F1-ATPase determined with 25 micromolar cruent... -
+
Open data
-
Basic information
Entry | ![]() | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of yeast F1-ATPase determined with 25 micromolar cruentaren A | ||||||||||||||||||
![]() | Sharpened map. | ||||||||||||||||||
![]() |
| ||||||||||||||||||
![]() | F1-ATPase / ATP Synthase / cruentaren A / drug development / HYDROLASE | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.5 Å | ||||||||||||||||||
![]() | Guo H / Rubinstein JL | ||||||||||||||||||
Funding support | ![]() ![]()
| ||||||||||||||||||
![]() | ![]() Title: CryoEM Structure with ATP Synthase Enables Late-Stage Diversification of Cruentaren A. Authors: Xiaozheng Dou / Hui Guo / Terin D'Amico / Leah Abdallah / Chitra Subramanian / Bhargav A Patel / Mark Cohen / John L Rubinstein / Brian S J Blagg / ![]() ![]() Abstract: Cruentaren A is a natural product that exhibits potent antiproliferative activity against various cancer cell lines, yet its binding site within ATP synthase remained unknown, thus limiting the ...Cruentaren A is a natural product that exhibits potent antiproliferative activity against various cancer cell lines, yet its binding site within ATP synthase remained unknown, thus limiting the development of improved analogues as anticancer agents. Herein, we report the cryogenic electron microscopy (cryoEM) structure of cruentaren A bound to ATP synthase, which allowed the design of new inhibitors through semisynthetic modification. Examples of cruentaren A derivatives include a trans-alkene isomer, which was found to exhibit similar activity to cruentaren A against three cancer cell lines as well as several other analogues that retained potent inhibitory activity. Together, these studies provide a foundation for the generation of cruentaren A derivatives as potential therapeutics for the treatment of cancer. | ||||||||||||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 118 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 19.8 KB 19.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12 KB | Display | ![]() |
Images | ![]() | 66.2 KB | ||
Masks | ![]() | 125 MB | ![]() | |
Filedesc metadata | ![]() | 4.8 KB | ||
Others | ![]() ![]() ![]() | 62.2 MB 115.9 MB 115.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 18.9 KB | Display | |
Data in CIF | ![]() | 23.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Sharpened map. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.04622 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: Unsharpened map.
File | emd_28819_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Unsharpened map. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map 1
File | emd_28819_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map 2
File | emd_28819_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Yeast F1-ATPase with 25 micromolar cruentaren A
Entire | Name: Yeast F1-ATPase with 25 micromolar cruentaren A |
---|---|
Components |
|
-Supramolecule #1: Yeast F1-ATPase with 25 micromolar cruentaren A
Supramolecule | Name: Yeast F1-ATPase with 25 micromolar cruentaren A / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 400 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 15 mg/mL |
---|---|
Buffer | pH: 7.4 |
Grid | Model: Homemade / Material: COPPER/RHODIUM / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Support film - Film thickness: 35 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 120 sec. / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: LEICA EM GP |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number real images: 345 / Average exposure time: 7.4 sec. / Average electron dose: 37.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated magnification: 133815 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 75000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
+
Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Source name: PDB / Chain - Initial model type: experimental model |
---|---|
Refinement | Space: RECIPROCAL / Protocol: RIGID BODY FIT |