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Yorodumi- PDB-7dv6: Discovery of Functionally Selective Transforming Growth Factor be... -
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-Basic information
Entry | Database: PDB / ID: 7dv6 | ||||||
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Title | Discovery of Functionally Selective Transforming Growth Factor beta Type II Receptor (TGF-beta RII) Inhibitors as Anti-Fibrosis Agents | ||||||
Components | TGF-beta receptor type-2 | ||||||
Keywords | IMMUNE SYSTEM / Inhibitor / Complex | ||||||
Function / homology | Function and homology information positive regulation of tolerance induction to self antigen / positive regulation of B cell tolerance induction / inferior endocardial cushion morphogenesis / transforming growth factor beta receptor activity, type II / bronchus morphogenesis / mammary gland morphogenesis / lens fiber cell apoptotic process / growth plate cartilage chondrocyte growth / tricuspid valve morphogenesis / TGFBR2 MSI Frameshift Mutants in Cancer ...positive regulation of tolerance induction to self antigen / positive regulation of B cell tolerance induction / inferior endocardial cushion morphogenesis / transforming growth factor beta receptor activity, type II / bronchus morphogenesis / mammary gland morphogenesis / lens fiber cell apoptotic process / growth plate cartilage chondrocyte growth / tricuspid valve morphogenesis / TGFBR2 MSI Frameshift Mutants in Cancer / activin receptor activity / miRNA transport / type III transforming growth factor beta receptor binding / transforming growth factor beta ligand-receptor complex / Langerhans cell differentiation / aorta morphogenesis / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity / secondary palate development / cardiac left ventricle morphogenesis / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / endocardial cushion fusion / positive regulation of T cell tolerance induction / membranous septum morphogenesis / lung lobe morphogenesis / positive regulation of NK T cell differentiation / regulation of stem cell proliferation / TGFBR1 LBD Mutants in Cancer / myeloid dendritic cell differentiation / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / activin binding / type I transforming growth factor beta receptor binding / positive regulation of CD4-positive, alpha-beta T cell proliferation / outflow tract septum morphogenesis / SMAD protein signal transduction / regulation of stem cell differentiation / glycosaminoglycan binding / kinase activator activity / transforming growth factor beta binding / response to cholesterol / embryonic cranial skeleton morphogenesis / aortic valve morphogenesis / lens development in camera-type eye / atrioventricular valve morphogenesis / embryonic hemopoiesis / positive regulation of mesenchymal cell proliferation / trachea formation / artery morphogenesis / smoothened signaling pathway / branching involved in blood vessel morphogenesis / ventricular septum morphogenesis / activation of protein kinase activity / roof of mouth development / positive regulation of epithelial cell migration / blood vessel development / heart looping / outflow tract morphogenesis / SMAD binding / TGF-beta receptor signaling activates SMADs / positive regulation of SMAD protein signal transduction / epithelial to mesenchymal transition / vasculogenesis / positive regulation of epithelial to mesenchymal transition / gastrulation / Notch signaling pathway / Downregulation of TGF-beta receptor signaling / transforming growth factor beta receptor signaling pathway / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / caveola / brain development / cellular response to growth factor stimulus / positive regulation of angiogenesis / UCH proteinases / positive regulation of reactive oxygen species metabolic process / heart development / regulation of cell population proliferation / regulation of gene expression / in utero embryonic development / molecular adaptor activity / receptor complex / response to xenobiotic stimulus / membrane raft / phosphorylation / external side of plasma membrane / apoptotic process / positive regulation of cell population proliferation / extracellular space / extracellular region / ATP binding / membrane / metal ion binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.39 Å | ||||||
Authors | Nishihata, J. / Nomura, A. / Miwa, S. / Doi, S. / Adachi, T. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2021 Title: Discovery of Selective Transforming Growth Factor beta Type II Receptor Inhibitors as Antifibrosis Agents. Authors: Miwa, S. / Yokota, M. / Ueyama, Y. / Maeda, K. / Ogoshi, Y. / Seki, N. / Ogawa, N. / Nishihata, J. / Nomura, A. / Adachi, T. / Kitao, Y. / Nozawa, K. / Ishikawa, T. / Ukaji, Y. / Shiozaki, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7dv6.cif.gz | 142.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7dv6.ent.gz | 108.3 KB | Display | PDB format |
PDBx/mmJSON format | 7dv6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7dv6_validation.pdf.gz | 786.3 KB | Display | wwPDB validaton report |
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Full document | 7dv6_full_validation.pdf.gz | 789.9 KB | Display | |
Data in XML | 7dv6_validation.xml.gz | 15.8 KB | Display | |
Data in CIF | 7dv6_validation.cif.gz | 22.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dv/7dv6 ftp://data.pdbj.org/pub/pdb/validation_reports/dv/7dv6 | HTTPS FTP |
-Related structure data
Related structure data | 5e8vS S: Starting model for refinement |
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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: 36787.703 Da / Num. of mol.: 1 / Mutation: E431A,R433A,E485A,K488A,R493A,R495A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TGFBR2 / Production host: Escherichia coli (E. coli) References: UniProt: P37173, receptor protein serine/threonine kinase |
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#2: Chemical | ChemComp-HJF / |
#3: 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: 2.5 Å3/Da / Density % sol: 50.73 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 12-22% PEG4000,3% Ethylene Glycol,16% glycerol, 160 mM MgCl2, 80 mM TrisHCl at pH 7.5-9.3,The 9.2 mg/mL of TGFbetaRII protein was incubated with 1mM compound at 277K for 1-2 hr PH range: 7.5-9.3 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER2 X 4M / Detector: PIXEL / Date: Jun 8, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.39→48.53 Å / Num. obs: 15148 / % possible obs: 99.9 % / Redundancy: 6.7 % / CC1/2: 0.998 / Rmerge(I) obs: 0.082 / Net I/σ(I): 19 |
Reflection shell | Resolution: 2.39→2.48 Å / Redundancy: 6.9 % / Rmerge(I) obs: 0.27 / Mean I/σ(I) obs: 7.6 / Num. unique obs: 1554 / CC1/2: 0.895 / % possible all: 99.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5E8V Resolution: 2.39→28.81 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.924 / SU B: 11.985 / SU ML: 0.148 / Cross valid method: THROUGHOUT / ESU R: 0.328 / ESU R Free: 0.234 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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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: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 46.599 Å2
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Refinement step | Cycle: 1 / Resolution: 2.39→28.81 Å
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