+Open data
-Basic information
Entry | Database: PDB / ID: 1py5 | ||||||
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Title | Crystal Structure of TGF-beta receptor I kinase with inhibitor | ||||||
Components | TGF-beta receptor type I | ||||||
Keywords | TRANSFERASE / TGF-beta / receptor I / kinase | ||||||
Function / homology | Function and homology information extracellular structure organization / epicardium morphogenesis / parathyroid gland development / myofibroblast differentiation / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / positive regulation of tight junction disassembly / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / positive regulation of mesenchymal stem cell proliferation ...extracellular structure organization / epicardium morphogenesis / parathyroid gland development / myofibroblast differentiation / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / positive regulation of tight junction disassembly / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / positive regulation of mesenchymal stem cell proliferation / transforming growth factor beta receptor activity / 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 / positive regulation of extracellular matrix assembly / germ cell migration / 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 / endothelial cell proliferation / artery morphogenesis / negative regulation of chondrocyte differentiation / collagen fibril organization / endothelial cell activation / skeletal system morphogenesis / lens development in camera-type eye / anterior/posterior pattern specification / positive regulation of filopodium assembly / ventricular septum morphogenesis / negative regulation of endothelial cell proliferation / roof of mouth development / SMAD binding / TGF-beta receptor signaling activates SMADs / positive regulation of SMAD protein signal transduction / blastocyst development / regulation of protein ubiquitination / bicellular tight junction / endothelial cell migration / 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 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / thymus development / 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 / positive regulation of cell migration / intracellular signal transduction / 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: 2.3 Å | ||||||
Authors | Zhang, F. / Sawyer, J.S. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2004 Title: Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain. Authors: Sawyer, J.S. / Beight, D.W. / Britt, K.S. / Anderson, B.D. / Campbell, R.M. / Goodson, T. / Herron, D.K. / Li, H.Y. / McMillen, W.T. / Mort, N. / Parsons, S. / Smith, E.C. / Wagner, J.R. / ...Authors: Sawyer, J.S. / Beight, D.W. / Britt, K.S. / Anderson, B.D. / Campbell, R.M. / Goodson, T. / Herron, D.K. / Li, H.Y. / McMillen, W.T. / Mort, N. / Parsons, S. / Smith, E.C. / Wagner, J.R. / Yan, L. / Zhang, F. / Yingling, J.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1py5.cif.gz | 78.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1py5.ent.gz | 56.9 KB | Display | PDB format |
PDBx/mmJSON format | 1py5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/py/1py5 ftp://data.pdbj.org/pub/pdb/validation_reports/py/1py5 | HTTPS FTP |
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-Related structure data
Related structure data | 1rw8C 1b6cS S: Starting model for refinement 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: 37102.590 Da / Num. of mol.: 1 / Fragment: Truncated kinase domain, residues 175-500 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TGFBR1 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P36897, EC: 2.7.1.37 |
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#2: Chemical | ChemComp-SO4 / |
#3: Chemical | ChemComp-PY1 / |
#4: 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 Å3/Da / Density % sol: 38.38 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.6 Details: Tris, ATP, MgCl2, DTT, Hexanediol, PEG4000, LiSO4, pH 7.6, VAPOR DIFFUSION, HANGING DROP, temperature 298.0K |
-Data collection
Diffraction | Mean temperature: 200 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: MARRESEARCH / Detector: CCD / Date: Jun 10, 2000 / Details: mirrors |
Radiation | Monochromator: Yale Mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→20 Å / Num. all: 13208 / Num. obs: 13178 / % possible obs: 99.7 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 6 % / Biso Wilson estimate: 17.3 Å2 / Rmerge(I) obs: 0.09 / Net I/σ(I): 8 |
Reflection shell | Resolution: 2.3→2.44 Å / Redundancy: 4 % / Rmerge(I) obs: 0.185 / Mean I/σ(I) obs: 5 / Num. unique all: 1607 / % possible all: 74.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1B6C Resolution: 2.3→20 Å / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / σ(F): 1 / Stereochemistry target values: Engh & Huber / Details: Used weighted full matrix least squares procedure
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Displacement parameters | Biso mean: 21.4 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.3→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.44 Å / Rfactor Rfree error: 0.041
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