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Yorodumi- PDB-8pqi: PDGFRA T674I mutant kinase domain in complex with avapritinib der... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8pqi | |||||||||||||||
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Title | PDGFRA T674I mutant kinase domain in complex with avapritinib derivative 9 | |||||||||||||||
Components | Platelet-derived growth factor receptor alpha | |||||||||||||||
Keywords | TRANSFERASE / PDGFRA protein kinase / avapritinib / inhibitor / tyrosine kinase / transmembrane receptor / platelet-derived growth factor receptor alpha / PDGF / platelet-derived growth factor / GIST / gastrointestinal stromal tumors / gatekeeper mutant / P16234 | |||||||||||||||
Function / homology | Function and homology information platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor receptor-alpha signaling pathway / Imatinib-resistant PDGFR mutants / Sunitinib-resistant PDGFR mutants / Regorafenib-resistant PDGFR mutants / Sorafenib-resistant PDGFR mutants / PDGFR mutants bind TKIs / metanephric glomerular capillary formation / regulation of mesenchymal stem cell differentiation / luteinization ...platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor receptor-alpha signaling pathway / Imatinib-resistant PDGFR mutants / Sunitinib-resistant PDGFR mutants / Regorafenib-resistant PDGFR mutants / Sorafenib-resistant PDGFR mutants / PDGFR mutants bind TKIs / metanephric glomerular capillary formation / regulation of mesenchymal stem cell differentiation / luteinization / positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway / platelet-derived growth factor binding / embryonic skeletal system morphogenesis / vascular endothelial growth factor binding / retina vasculature development in camera-type eye / cardiac myofibril assembly / embryonic digestive tract morphogenesis / vascular endothelial growth factor receptor activity / Leydig cell differentiation / cell activation / male genitalia development / Signaling by PDGF / positive regulation of chemotaxis / signal transduction involved in regulation of gene expression / embryonic cranial skeleton morphogenesis / platelet-derived growth factor receptor binding / face morphogenesis / estrogen metabolic process / white fat cell differentiation / adrenal gland development / roof of mouth development / odontogenesis of dentin-containing tooth / microvillus / platelet-derived growth factor receptor signaling pathway / negative regulation of platelet activation / transmembrane receptor protein tyrosine kinase activity / hematopoietic progenitor cell differentiation / : / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / positive regulation of calcium-mediated signaling / Downstream signal transduction / cellular response to amino acid stimulus / extracellular matrix organization / cell chemotaxis / lung development / receptor protein-tyrosine kinase / regulation of actin cytoskeleton organization / wound healing / cellular response to reactive oxygen species / peptidyl-tyrosine phosphorylation / cilium / Constitutive Signaling by Aberrant PI3K in Cancer / platelet aggregation / positive regulation of fibroblast proliferation / cell junction / PIP3 activates AKT signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein autophosphorylation / in utero embryonic development / receptor complex / positive regulation of ERK1 and ERK2 cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of cell migration / protein kinase activity / external side of plasma membrane / positive regulation of cell population proliferation / endoplasmic reticulum membrane / protein-containing complex binding / Golgi apparatus / protein homodimerization activity / protein-containing complex / nucleoplasm / ATP binding / membrane / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å | |||||||||||||||
Authors | Teuber, A. / Kleinboelting, S. / Mueller, M.P. / Rauh, D. | |||||||||||||||
Funding support | European Union, Germany, 4items
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Citation | Journal: Nat Commun / Year: 2024 Title: Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA. Authors: Teuber, A. / Schulz, T. / Fletcher, B.S. / Gontla, R. / Muhlenberg, T. / Zischinsky, M.L. / Niggenaber, J. / Weisner, J. / Kleinbolting, S.B. / Lategahn, J. / Sievers, S. / Muller, M.P. / Bauer, S. / Rauh, D. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8pqi.cif.gz | 160.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8pqi.ent.gz | 103.9 KB | Display | PDB format |
PDBx/mmJSON format | 8pqi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8pqi_validation.pdf.gz | 677.2 KB | Display | wwPDB validaton report |
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Full document | 8pqi_full_validation.pdf.gz | 680.3 KB | Display | |
Data in XML | 8pqi_validation.xml.gz | 13.2 KB | Display | |
Data in CIF | 8pqi_validation.cif.gz | 16.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pq/8pqi ftp://data.pdbj.org/pub/pdb/validation_reports/pq/8pqi | HTTPS FTP |
-Related structure data
Related structure data | 8pq9C 8pqaC 8pqbC 8pqcC 8pqdC 8pqeC 8pqfC 8pqgC 8pqhC 8pqjC 8pqkC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
Experimental dataset #1 | Data reference: 10.18430/m38pqi / Data set type: diffraction image data / Details: https://www.proteindiffraction.org/project/8PQI/ |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 40226.371 Da / Num. of mol.: 1 / Mutation: T674I Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDGFRA, PDGFR2, RHEPDGFRA / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P16234, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-9OO / ( |
#3: Chemical | ChemComp-PEG / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.04 Å3/Da / Density % sol: 39.82 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, hanging drop / Details: 5 mg/mL, 5% PEG3350, 200 mM KCl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Dec 13, 2021 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→46.63 Å / Num. obs: 12552 / % possible obs: 98.3 % / Redundancy: 13.05 % / Biso Wilson estimate: 68.5 Å2 / CC1/2: 0.998 / Rrim(I) all: 0.118 / Net I/σ(I): 12.39 |
Reflection shell | Resolution: 2.6→2.7 Å / Redundancy: 13.54 % / Mean I/σ(I) obs: 1.8 / Num. unique obs: 1309 / CC1/2: 0.876 / Rrim(I) all: 1.607 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.6→46.63 Å / SU ML: 0.3892 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 34.0342 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 78.93 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.6→46.63 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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