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Yorodumi- PDB-2qu5: Crystal structure of the VEGFR2 kinase domain in complex with a b... -
+Open data
-Basic information
Entry | Database: PDB / ID: 2qu5 | ||||||
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Title | Crystal structure of the VEGFR2 kinase domain in complex with a benzimidazole inhibitor | ||||||
Components | Vascular endothelial growth factor receptor 2 | ||||||
Keywords | TRANSFERASE / receptor tyrosinse kinase / KDR / 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 / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / endothelium development / 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 / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / endothelium development / endocardium development / vascular wound healing / regulation of hematopoietic progenitor cell differentiation / vascular endothelial growth factor receptor activity / post-embryonic camera-type eye morphogenesis / endothelial cell differentiation / positive regulation of vasculogenesis / mesenchymal cell proliferation / lymph vessel development / positive regulation of BMP signaling pathway / surfactant homeostasis / cell migration involved in sprouting angiogenesis / epithelial cell maturation / anchoring junction / positive regulation of positive chemotaxis / embryonic hemopoiesis / vascular endothelial growth factor signaling pathway / positive regulation of mesenchymal cell proliferation / positive regulation of endothelial cell chemotaxis / branching involved in blood vessel morphogenesis / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of mitochondrial fission / positive regulation of mitochondrial depolarization / lung alveolus development / positive regulation of stem cell proliferation / positive regulation of nitric-oxide synthase biosynthetic process / growth factor binding / sorting endosome / 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 / vasculogenesis / Integrin cell surface interactions / 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 / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of endothelial cell migration / transmembrane receptor protein tyrosine kinase activity / VEGFR2 mediated cell proliferation / epithelial cell proliferation / stem cell proliferation / 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 / positive regulation of ERK1 and ERK2 cascade / early endosome / receptor complex / endosome / positive regulation of cell migration / cadherin binding / positive regulation of protein phosphorylation / membrane raft / 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 / molecular replacement / Resolution: 2.95 Å | ||||||
Authors | Whittington, D.A. / Kim, J.L. / Long, A.M. / Rose, P. / Gu, Y. / Zhao, H. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2007 Title: Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors. Authors: Potashman, M.H. / Bready, J. / Coxon, A. / Demelfi, T.M. / Dipietro, L. / Doerr, N. / Elbaum, D. / Estrada, J. / Gallant, P. / Germain, J. / Gu, Y. / Harmange, J.C. / Kaufman, S.A. / ...Authors: Potashman, M.H. / Bready, J. / Coxon, A. / Demelfi, T.M. / Dipietro, L. / Doerr, N. / Elbaum, D. / Estrada, J. / Gallant, P. / Germain, J. / Gu, Y. / Harmange, J.C. / Kaufman, S.A. / Kendall, R. / Kim, J.L. / Kumar, G.N. / Long, A.M. / Neervannan, S. / Patel, V.F. / Polverino, A. / Rose, P. / Plas, S.V. / Whittington, D. / Zanon, R. / Zhao, H. | ||||||
History |
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Remark 999 | Sequence This is a deletion mutant (residues 940-989) of UniProt entry P35968. |
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2qu5.cif.gz | 74.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2qu5.ent.gz | 53.6 KB | Display | PDB format |
PDBx/mmJSON format | 2qu5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 2qu5_validation.pdf.gz | 672.1 KB | Display | wwPDB validaton report |
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Full document | 2qu5_full_validation.pdf.gz | 676.5 KB | Display | |
Data in XML | 2qu5_validation.xml.gz | 13.2 KB | Display | |
Data in CIF | 2qu5_validation.cif.gz | 16.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qu/2qu5 ftp://data.pdbj.org/pub/pdb/validation_reports/qu/2qu5 | HTTPS FTP |
-Related structure data
Related structure data | 2qu6C 2p2iS C: citing same article (ref.) 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: 36284.586 Da / Num. of mol.: 1 / Fragment: kinase domain / 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 |
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#2: Chemical | ChemComp-276 / |
#3: 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: 3.89 Å3/Da / Density % sol: 68.39 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8.2 Details: PEG 4000, lithum sulfate, Tris, pH 8.2, VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 |
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Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Relative weight: 1 |
Reflection | Resolution: 2.95→30 Å / Num. obs: 12783 / % possible obs: 99.9 % / Observed criterion σ(I): -3 / Redundancy: 7.1 % / Biso Wilson estimate: 56 Å2 / Rmerge(I) obs: 0.081 / Χ2: 1.051 / Net I/σ(I): 23.9 |
Reflection shell | Resolution: 2.95→3.06 Å / Rmerge(I) obs: 0.47 / Mean I/σ(I) obs: 4.1 / Num. unique all: 1247 / Χ2: 0.808 / % possible all: 100 |
-Phasing
Phasing | Method: molecular replacement | ||||||
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Phasing MR | Rfactor: 0.444 / Cor.coef. Fo:Fc: 0.606
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 2P2I Resolution: 2.95→30 Å / Data cutoff high absF: 10000 / Data cutoff low absF: 0 / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Displacement parameters |
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.95→30 Å
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Refine LS restraints |
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