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Yorodumi- PDB-8edh: Identification of a class of WNK isoform-specific inhibitors thro... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8edh | |||||||||
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Title | Identification of a class of WNK isoform-specific inhibitors through high-throughput screening | |||||||||
Components | Serine/threonine-protein kinase WNK3 | |||||||||
Keywords | TRANSFERASE / inhibitor / WNK3 / kinase / complex | |||||||||
Function / homology | Function and homology information positive regulation of ion transmembrane transporter activity / negative regulation of pancreatic juice secretion / positive regulation of sodium ion transmembrane transporter activity / monoatomic ion homeostasis / regulation of calcium ion import / osmosensory signaling pathway / positive regulation of sodium ion transport / non-membrane-bounded organelle assembly / positive regulation of calcium ion transport / cellular hyperosmotic response ...positive regulation of ion transmembrane transporter activity / negative regulation of pancreatic juice secretion / positive regulation of sodium ion transmembrane transporter activity / monoatomic ion homeostasis / regulation of calcium ion import / osmosensory signaling pathway / positive regulation of sodium ion transport / non-membrane-bounded organelle assembly / positive regulation of calcium ion transport / cellular hyperosmotic response / cell volume homeostasis / regulation of monoatomic cation transmembrane transport / negative regulation of protein localization to plasma membrane / maintenance of blood-brain barrier / bicellular tight junction / positive regulation of protein localization to plasma membrane / molecular condensate scaffold activity / positive regulation of peptidyl-threonine phosphorylation / protein localization to plasma membrane / adherens junction / peptidyl-threonine phosphorylation / Stimuli-sensing channels / protein autophosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / negative regulation of apoptotic process / ATP binding / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.111 Å | |||||||||
Authors | Akella, R. / Goldsmith, E.J. | |||||||||
Funding support | United States, 1items
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Citation | Journal: Drug Des Devel Ther / Year: 2023 Title: Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening. Authors: Chlebowicz, J. / Akella, R. / Humphreys, J.M. / He, H. / Kannangara, A.R. / Wei, S. / Posner, B. / Goldsmith, E.J. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8edh.cif.gz | 128.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8edh.ent.gz | 93.1 KB | Display | PDB format |
PDBx/mmJSON format | 8edh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ed/8edh ftp://data.pdbj.org/pub/pdb/validation_reports/ed/8edh | HTTPS FTP |
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-Related structure data
Related structure data | 5fpqS S: Starting model for refinement |
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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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2 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: ALA / End label comp-ID: ALA / Refine code: 1 / Auth asym-ID: A / Label asym-ID: A / Auth seq-ID: 137 - 406 / Label seq-ID: 20 - 289
NCS ensembles : (Details: Local NCS retraints between domains: 1 2) |
-Components
#1: Protein | Mass: 33637.930 Da / Num. of mol.: 2 / Mutation: S308A Source method: isolated from a genetically manipulated source Details: Kinase domain of WNK3 with S308A mutation / Source: (gene. exp.) Homo sapiens (human) / Gene: WNK3, KIAA1566, PRKWNK3 / Production host: Escherichia coli BL21 (bacteria) References: UniProt: Q9BYP7, non-specific serine/threonine protein kinase #2: Chemical | ChemComp-WGK / | #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.78 Å3/Da / Density % sol: 56 % / Description: plates |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 0.1M Sodium Malonate pH 5.0 and 12% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97925 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Mar 15, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97925 Å / Relative weight: 1 |
Reflection | Resolution: 3.11→27.8 Å / Num. obs: 13357 / % possible obs: 86 % / Redundancy: 4.8 % / Biso Wilson estimate: 44.4 Å2 / CC1/2: 0.95 / Rpim(I) all: 0.04 / Rsym value: 0.07 / Net I/σ(I): 8.4 |
Reflection shell | Resolution: 3.11→4.8 Å / Redundancy: 4.9 % / Num. unique obs: 674 / CC1/2: 0.4 / % possible all: 98.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5FPQ Resolution: 3.111→26.485 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.814 / WRfactor Rfree: 0.285 / WRfactor Rwork: 0.178 / SU B: 27.783 / SU ML: 0.457 / Average fsc free: 0.9415 / Average fsc work: 0.9742 / Cross valid method: FREE R-VALUE / ESU R Free: 0.665 / Details: Hydrogens have not been used
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 69.718 Å2
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Refinement step | Cycle: LAST / Resolution: 3.111→26.485 Å
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Refine LS restraints |
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Refine LS restraints NCS |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20
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