+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16510 | |||||||||
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Title | AQP7_inhibitor | |||||||||
Map data | ||||||||||
Sample |
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Keywords | aquaglyceroporin / glycerol channel / dimer of tetramers / inhibitor / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information Transport of glycerol from adipocytes to the liver by Aquaporins / glycerol channel activity / urea transmembrane transporter activity / Passive transport by Aquaporins / glycerol transmembrane transport / water transport / water channel activity / lipid droplet / cytoplasmic vesicle membrane / cell-cell junction ...Transport of glycerol from adipocytes to the liver by Aquaporins / glycerol channel activity / urea transmembrane transporter activity / Passive transport by Aquaporins / glycerol transmembrane transport / water transport / water channel activity / lipid droplet / cytoplasmic vesicle membrane / cell-cell junction / cell cortex / basolateral plasma membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Huang P / Venskutonyte R / Gourdon P / Lindkvist-Petersson K | |||||||||
Funding support | Sweden, 2 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2024 Title: Molecular basis for human aquaporin inhibition. Authors: Peng Huang / Hannah Åbacka / Carter J Wilson / Malene Lykke Wind / Michael Rűtzler / Anna Hagström-Andersson / Pontus Gourdon / Bert L de Groot / Raminta Venskutonytė / Karin Lindkvist-Petersson / Abstract: Cancer invasion and metastasis are known to be potentiated by the expression of aquaporins (AQPs). Likewise, the expression levels of AQPs have been shown to be prognostic for survival in patients ...Cancer invasion and metastasis are known to be potentiated by the expression of aquaporins (AQPs). Likewise, the expression levels of AQPs have been shown to be prognostic for survival in patients and have a role in tumor growth, edema, angiogenesis, and tumor cell migration. Thus, AQPs are key players in cancer biology and potential targets for drug development. Here, we present the single-particle cryo-EM structure of human AQP7 at 3.2-Å resolution in complex with the specific inhibitor compound Z433927330. The structure in combination with MD simulations shows that the inhibitor binds to the endofacial side of AQP7. In addition, cancer cells treated with Z433927330 show reduced proliferation. The data presented here serve as a framework for the development of AQP inhibitors. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16510.map.gz | 97.1 MB | EMDB map data format | |
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Header (meta data) | emd-16510-v30.xml emd-16510.xml | 18.6 KB 18.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16510_fsc.xml | 9.9 KB | Display | FSC data file |
Images | emd_16510.png | 31.5 KB | ||
Masks | emd_16510_msk_1.map | 103 MB | Mask map | |
Filedesc metadata | emd-16510.cif.gz | 6.3 KB | ||
Others | emd_16510_half_map_1.map.gz emd_16510_half_map_2.map.gz | 95.3 MB 95.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16510 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16510 | HTTPS FTP |
-Validation report
Summary document | emd_16510_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_16510_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_16510_validation.xml.gz | 18.3 KB | Display | |
Data in CIF | emd_16510_validation.cif.gz | 23.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16510 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16510 | HTTPS FTP |
-Related structure data
Related structure data | 8c9hMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_16510.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.8464 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_16510_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_16510_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_16510_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : AQP7 dimer of tetramers with inhibitor
Entire | Name: AQP7 dimer of tetramers with inhibitor |
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Components |
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-Supramolecule #1: AQP7 dimer of tetramers with inhibitor
Supramolecule | Name: AQP7 dimer of tetramers with inhibitor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 / Details: sample was prepared in GDN detergent |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Aquaporin-7
Macromolecule | Name: Aquaporin-7 / type: protein_or_peptide / ID: 1 / Details: LIG represents the inhibitor / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.264395 KDa |
Recombinant expression | Organism: Komagataella pastoris (fungus) |
Sequence | String: MVQASGHRRS TRGSKMVSWS VIAKIQEILQ RKMVREFLAE FMSTYVMMVF GLGSVAHMVL NKKYGSYLGV NLGFGFGVTM GVHVAGRIS GAHMNAAVTF ANCALGRVPW RKFPVYVLGQ FLGSFLAAAT IYSLFYTAIL HFSGGQLMVT GPVATAGIFA T YLPDHMTL ...String: MVQASGHRRS TRGSKMVSWS VIAKIQEILQ RKMVREFLAE FMSTYVMMVF GLGSVAHMVL NKKYGSYLGV NLGFGFGVTM GVHVAGRIS GAHMNAAVTF ANCALGRVPW RKFPVYVLGQ FLGSFLAAAT IYSLFYTAIL HFSGGQLMVT GPVATAGIFA T YLPDHMTL WRGFLNEAWL TGMLQLCLFA ITDQENNPAL PGTEALVIGI LVVIIGVSLG MNTGYAINPS RDLPPRIFTF IA GWGKQVF SNGENWWWVP VVAPLLGAYL GGIIYLVFIG STIPREPLKL EDSVAYEDHG ITVLPKMGSH EPTISPLTPV SVS PANRSS VHPAPPLHES MALEHF UniProtKB: Aquaporin-7 |
-Macromolecule #2: ethyl 4-[(4-pyrazol-1-ylphenyl)methylcarbamoylamino]benzoate
Macromolecule | Name: ethyl 4-[(4-pyrazol-1-ylphenyl)methylcarbamoylamino]benzoate type: ligand / ID: 2 / Number of copies: 8 / Formula: T60 |
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Molecular weight | Theoretical: 364.398 Da |
Chemical component information | ChemComp-T60: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Details: 20mA for glow discharge | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK II / Details: 3s blot, 3s wait, 0s drain time, 0 blot force. | ||||||||||||
Details | 25uM inhibitor was supplemented into protein solution before grid freezing. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 9002 / Average exposure time: 2.16 sec. / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 105000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Details | Initial model (PDB ID:8AMX) was fitted locally into map by Chimera. |
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Refinement | Space: REAL / Protocol: RIGID BODY FIT / Overall B value: 108 |
Output model | PDB-8c9h: |