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Yorodumi- PDB-3b8q: Crystal structure of the VEGFR2 kinase domain in complex with a n... -
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-Basic information
Entry | Database: PDB / ID: 3b8q | ||||||
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Title | Crystal structure of the VEGFR2 kinase domain in complex with a naphthamide inhibitor | ||||||
Components | Vascular endothelial growth factor receptor 2VEGF receptor | ||||||
Keywords | TRANSFERASE / receptor tyrosine kinase / angiogenesis / ATP-binding / Developmental protein / Differentiation / Glycoprotein / Host-virus interaction / Immunoglobulin domain / Membrane / Nucleotide-binding / Phosphorylation / Polymorphism / Transmembrane / Tyrosine-protein kinase | ||||||
Function / homology | Function and homology information blood vessel endothelial cell differentiation / cellular response to hydrogen sulfide / regulation of bone development / Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / vascular endothelial growth factor binding / Neurophilin interactions with VEGF and VEGFR / endothelium development / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / endocardium development ...blood vessel endothelial cell differentiation / cellular response to hydrogen sulfide / regulation of bone development / Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / vascular endothelial growth factor binding / Neurophilin interactions with VEGF and VEGFR / endothelium development / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / endocardium development / vascular wound healing / vascular endothelial growth factor receptor activity / regulation of hematopoietic progenitor cell differentiation / post-embryonic camera-type eye morphogenesis / endothelial cell differentiation / mesenchymal cell proliferation / positive regulation of vasculogenesis / lymph vessel development / positive regulation of BMP signaling pathway / surfactant homeostasis / cell migration involved in sprouting angiogenesis / anchoring junction / epithelial cell maturation / positive regulation of positive chemotaxis / embryonic hemopoiesis / vascular endothelial growth factor signaling pathway / positive regulation of endothelial cell chemotaxis / positive regulation of mesenchymal cell proliferation / positive regulation of mitochondrial depolarization / branching involved in blood vessel morphogenesis / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of mitochondrial fission / lung alveolus development / positive regulation of stem cell proliferation / positive regulation of nitric-oxide synthase biosynthetic process / sorting endosome / growth factor binding / positive regulation of focal adhesion assembly / regulation of MAPK cascade / semaphorin-plexin signaling pathway / positive regulation of macroautophagy / : / positive regulation of blood vessel endothelial cell migration / cellular response to vascular endothelial growth factor stimulus / cell fate commitment / calcium ion homeostasis / Integrin cell surface interactions / vasculogenesis / vascular endothelial growth factor receptor signaling pathway / coreceptor activity / negative regulation of endothelial cell apoptotic process / peptidyl-tyrosine autophosphorylation / ovarian follicle development / positive regulation of endothelial cell proliferation / transmembrane receptor protein tyrosine kinase activity / positive regulation of endothelial cell migration / VEGFR2 mediated cell proliferation / epithelial cell proliferation / stem cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / Hsp90 protein binding / receptor protein-tyrosine kinase / VEGFA-VEGFR2 Pathway / peptidyl-tyrosine phosphorylation / positive regulation of angiogenesis / cell migration / integrin binding / cell junction / regulation of cell shape / protein tyrosine kinase activity / angiogenesis / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / early endosome / positive regulation of ERK1 and ERK2 cascade / receptor complex / endosome / positive regulation of cell migration / cadherin binding / membrane raft / positive regulation of protein phosphorylation / external side of plasma membrane / negative regulation of gene expression / positive regulation of cell population proliferation / negative regulation of apoptotic process / Golgi apparatus / endoplasmic reticulum / extracellular region / ATP binding / identical protein binding / nucleus / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.75 Å | ||||||
Authors | Whittington, D.A. / Long, A.M. / Gu, Y. / Zhao, H. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2008 Title: Naphthamides as Novel and Potent Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: Design, Synthesis and Evaluation Authors: Harmange, J.C. / Weiss, M.M. / Germain, J. / Polverino, A.J. / Borg, G. / Bready, J. / Chen, D. / Choquette, D. / Coxon, A. / DeMelfi, T. / DiPietro, L. / Doerr, N. / Estrada, J. / Flynn, J. ...Authors: Harmange, J.C. / Weiss, M.M. / Germain, J. / Polverino, A.J. / Borg, G. / Bready, J. / Chen, D. / Choquette, D. / Coxon, A. / DeMelfi, T. / DiPietro, L. / Doerr, N. / Estrada, J. / Flynn, J. / Graceffa, R.F. / Harriman, S.P. / Kaufman, S. / La, D.S. / Long, A. / Martin, M.W. / Neervannan, S. / Patel, V.F. / Potashman, M. / Regal, K. / Roveto, P.M. / Schrag, M.L. / Starnes, C. / Tasker, A. / Teffera, Y. / Wang, L. / White, R.D. / Whittington, D.A. / Zanon, R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3b8q.cif.gz | 128.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3b8q.ent.gz | 99.1 KB | Display | PDB format |
PDBx/mmJSON format | 3b8q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b8/3b8q ftp://data.pdbj.org/pub/pdb/validation_reports/b8/3b8q | HTTPS FTP |
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-Related structure data
Related structure data | 3be2C 2qu6S 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 36284.586 Da / Num. of mol.: 2 / Fragment: kinase domain; UNP residues 815-939, 990-1171 / Mutation: C817A, V916T, E990V Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KDR, FLK1 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P35968, receptor protein-tyrosine kinase #2: Chemical | #3: Water | ChemComp-HOH / | |
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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: 2.28 Å3/Da / Density % sol: 45.95 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion / pH: 8 Details: PEG 5000 MME, HEPES, sodium chloride, ammonium sulfate, isopropanol, beta-mercaptoethanol, pH 8.0, VAPOR DIFFUSION, temperature 277K |
-Data collection
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 |
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Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jun 28, 2004 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Relative weight: 1 |
Reflection | Resolution: 2.75→30 Å / Num. all: 17177 / Num. obs: 16164 / % possible obs: 94.1 % / Observed criterion σ(I): -3 / Redundancy: 3.6 % / Biso Wilson estimate: 39.6 Å2 / Rmerge(I) obs: 0.122 / Χ2: 1.077 |
Reflection shell | Resolution: 2.75→2.85 Å / Redundancy: 2.7 % / Rmerge(I) obs: 0.321 / Num. unique all: 1202 / Χ2: 0.688 / % possible all: 70.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 2QU6 Resolution: 2.75→30 Å / Data cutoff high absF: 10000 / Data cutoff low absF: 0 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Displacement parameters | Biso mean: 37.4 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.75→30 Å
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Refine LS restraints |
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