+Open data
-Basic information
Entry | Database: PDB / ID: 8c9h | |||||||||
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Title | AQP7_inhibitor | |||||||||
Components | Aquaporin-7 | |||||||||
Keywords | MEMBRANE PROTEIN / aquaglyceroporin / glycerol channel / dimer of tetramers / inhibitor | |||||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Huang, P. / Venskutonyte, R. / Gourdon, P. / Lindkvist-Petersson, K. | |||||||||
Funding support | Sweden, 2items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8c9h.cif.gz | 388.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8c9h.ent.gz | 318.7 KB | Display | PDB format |
PDBx/mmJSON format | 8c9h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8c9h_validation.pdf.gz | 1.9 MB | Display | wwPDB validaton report |
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Full document | 8c9h_full_validation.pdf.gz | 1.9 MB | Display | |
Data in XML | 8c9h_validation.xml.gz | 68.8 KB | Display | |
Data in CIF | 8c9h_validation.cif.gz | 94 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c9/8c9h ftp://data.pdbj.org/pub/pdb/validation_reports/c9/8c9h | HTTPS FTP |
-Related structure data
Related structure data | 16510MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 37264.395 Da / Num. of mol.: 8 Source method: isolated from a genetically manipulated source Details: LIG represents the inhibitor / Source: (gene. exp.) Homo sapiens (human) / Gene: AQP7, AQP7L, AQP9 / Production host: Komagataella pastoris (fungus) / References: UniProt: O14520 #2: Chemical | ChemComp-T60 / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: AQP7 dimer of tetramers with inhibitor / Type: COMPLEX / Details: sample was prepared in GDN detergent / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: Komagataella pastoris (fungus) | ||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: 25uM inhibitor was supplemented into protein solution before grid freezing. | ||||||||||||||||||||
Specimen support | Details: 20mA for glow discharge / Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: C-flat-1.2/1.3 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K / Details: 3s blot, 3s wait, 0s drain time, 0 blot force |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 600 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 2.16 sec. / Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9002 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 484660 / Details: applying template picking tool. | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: D4 (2x4 fold dihedral) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 16851 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 108 / Protocol: RIGID BODY FIT / Space: REAL Details: Initial model (PDB ID:8AMX) was fitted locally into map by Chimera. | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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