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Yorodumi- PDB-4x2g: Selection of fragments for kinase inhibitor design: decoration is key -
+Open data
-Basic information
Entry | Database: PDB / ID: 4x2g | ||||||
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Title | Selection of fragments for kinase inhibitor design: decoration is key | ||||||
Components | TGF-beta receptor type-1 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / TRANSFERASE / PROTEIN KINASE / INHIBITOR COMPLEX / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information extracellular structure organization / epicardium morphogenesis / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of tight junction disassembly / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity ...extracellular structure organization / epicardium morphogenesis / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / myofibroblast differentiation / positive regulation of tight junction disassembly / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity / positive regulation of mesenchymal stem cell proliferation / ventricular compact myocardium morphogenesis / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / positive regulation of vasculature development / regulation of epithelial to mesenchymal transition / activin receptor activity, type I / cardiac epithelial to mesenchymal transition / transforming growth factor beta receptor activity, type I / activin receptor complex / mesenchymal cell differentiation / neuron fate commitment / germ cell migration / positive regulation of extracellular matrix assembly / type II transforming growth factor beta receptor binding / TGFBR1 LBD Mutants in Cancer / angiogenesis involved in coronary vascular morphogenesis / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / pharyngeal system development / activin binding / coronary artery morphogenesis / activin receptor signaling pathway / filopodium assembly / ventricular trabecula myocardium morphogenesis / transforming growth factor beta binding / embryonic cranial skeleton morphogenesis / response to cholesterol / I-SMAD binding / negative regulation of chondrocyte differentiation / collagen fibril organization / endothelial cell proliferation / endothelial cell activation / skeletal system morphogenesis / lens development in camera-type eye / positive regulation of filopodium assembly / anterior/posterior pattern specification / artery morphogenesis / ventricular septum morphogenesis / roof of mouth development / TGF-beta receptor signaling activates SMADs / SMAD binding / negative regulation of endothelial cell proliferation / positive regulation of SMAD protein signal transduction / blastocyst development / regulation of protein ubiquitination / endothelial cell migration / bicellular tight junction / epithelial to mesenchymal transition / positive regulation of epithelial to mesenchymal transition / positive regulation of apoptotic signaling pathway / positive regulation of stress fiber assembly / cellular response to transforming growth factor beta stimulus / positive regulation of endothelial cell proliferation / Downregulation of TGF-beta receptor signaling / post-embryonic development / transforming growth factor beta receptor signaling pathway / negative regulation of cell migration / thymus development / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / kidney development / skeletal system development / cell motility / negative regulation of extrinsic apoptotic signaling pathway / wound healing / cellular response to growth factor stimulus / male gonad development / UCH proteinases / nervous system development / heart development / positive regulation of cell growth / regulation of gene expression / peptidyl-serine phosphorylation / in utero embryonic development / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / regulation of cell cycle / Ub-specific processing proteases / endosome / protein kinase activity / intracellular signal transduction / positive regulation of cell migration / membrane raft / protein serine/threonine kinase activity / apoptotic process / ubiquitin protein ligase binding / positive regulation of cell population proliferation / positive regulation of gene expression / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.51 Å | ||||||
Authors | Czodrowski, P. / Hoelzemann, G. / Barnickel, G. / Greiner, H. / Musil, D. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Selection of fragments for kinase inhibitor design: decoration is key. Authors: Czodrowski, P. / Holzemann, G. / Barnickel, G. / Greiner, H. / Musil, D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4x2g.cif.gz | 84 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4x2g.ent.gz | 61.5 KB | Display | PDB format |
PDBx/mmJSON format | 4x2g.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x2/4x2g ftp://data.pdbj.org/pub/pdb/validation_reports/x2/4x2g | HTTPS FTP |
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-Related structure data
Related structure data | 4x0mC 4x2fC 4x2jC 4x2kC 4x2nC 4x3jC C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 34882.148 Da / Num. of mol.: 1 / Fragment: UNP residues 200-503 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TGFBR1, ALK5, SKR4 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P36897, receptor protein serine/threonine kinase |
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#2: Chemical | ChemComp-3WK / |
#3: Chemical | ChemComp-SO4 / |
#4: Chemical | ChemComp-TRS / |
#5: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.12 Å3/Da / Density % sol: 41.96 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 0.1 M Tris-HCl, 240 mM Li2SO4, 24% PEG 4000, pH 7.5 PH range: 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Dec 13, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.51→22.11 Å / Num. obs: 46334 / % possible obs: 97.4 % / Redundancy: 7.2 % / Biso Wilson estimate: 14.92 Å2 / Rmerge(I) obs: 0.032 / Rsym value: 0.046 / Net I/σ(I): 30.4 |
Reflection shell | Resolution: 1.51→1.6 Å / Redundancy: 7.1 % / Rmerge(I) obs: 0.094 / Mean I/σ(I) obs: 12.5 / % possible all: 92.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: in-house model Resolution: 1.51→22.11 Å / Cor.coef. Fo:Fc: 0.9552 / Cor.coef. Fo:Fc free: 0.9533 / SU R Cruickshank DPI: 0.071 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.075 / SU Rfree Blow DPI: 0.072 / SU Rfree Cruickshank DPI: 0.069
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Displacement parameters | Biso max: 103.53 Å2 / Biso mean: 18.26 Å2 / Biso min: 6 Å2
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Refine analyze | Luzzati coordinate error obs: 0.136 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.51→22.11 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.51→1.55 Å / Total num. of bins used: 20
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