+Open data
-Basic information
Entry | Database: PDB / ID: 3efk | ||||||
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Title | Structure of c-Met with pyrimidone inhibitor 50 | ||||||
Components | Hepatocyte growth factor receptorC-Met | ||||||
Keywords | TRANSFERASE / c-Met / Kinase inhibitor pyrimidone / Alternative splicing / ATP-binding / Chromosomal rearrangement / Disease mutation / Glycoprotein / Kinase / Membrane / Nucleotide-binding / Phosphoprotein / Polymorphism / Proto-oncogene / Receptor / Transmembrane / Tyrosine-protein kinase | ||||||
Function / homology | Function and homology information hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / semaphorin receptor activity / positive regulation of endothelial cell chemotaxis ...hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / semaphorin receptor activity / positive regulation of endothelial cell chemotaxis / MET receptor recycling / pancreas development / MET activates PTPN11 / MET activates RAP1 and RAC1 / Sema4D mediated inhibition of cell attachment and migration / MET activates PI3K/AKT signaling / negative regulation of stress fiber assembly / negative regulation of Rho protein signal transduction / MET activates PTK2 signaling / branching morphogenesis of an epithelial tube / positive chemotaxis / negative regulation of thrombin-activated receptor signaling pathway / semaphorin-plexin signaling pathway / establishment of skin barrier / MET activates RAS signaling / phagocytosis / MECP2 regulates neuronal receptors and channels / positive regulation of microtubule polymerization / negative regulation of autophagy / basal plasma membrane / InlB-mediated entry of Listeria monocytogenes into host cell / liver development / molecular function activator activity / Negative regulation of MET activity / receptor protein-tyrosine kinase / neuron differentiation / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / PIP3 activates AKT signaling / nervous system development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / cell surface receptor signaling pathway / receptor complex / phosphorylation / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular region / ATP binding / membrane / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||
Authors | Bellon, S.F. / D'Angelo, N. / Whittington, D. / Dussault, I. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2008 Title: Design, synthesis, and biological evaluation of potent c-Met inhibitors. Authors: D'Angelo, N.D. / Bellon, S.F. / Booker, S.K. / Cheng, Y. / Coxon, A. / Dominguez, C. / Fellows, I. / Hoffman, D. / Hungate, R. / Kaplan-Lefko, P. / Lee, M.R. / Li, C. / Liu, L. / Rainbeau, E. ...Authors: D'Angelo, N.D. / Bellon, S.F. / Booker, S.K. / Cheng, Y. / Coxon, A. / Dominguez, C. / Fellows, I. / Hoffman, D. / Hungate, R. / Kaplan-Lefko, P. / Lee, M.R. / Li, C. / Liu, L. / Rainbeau, E. / Reider, P.J. / Rex, K. / Siegmund, A. / Sun, Y. / Tasker, A.S. / Xi, N. / Xu, S. / Yang, Y. / Zhang, Y. / Burgess, T.L. / Dussault, I. / Kim, T.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3efk.cif.gz | 123 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3efk.ent.gz | 95.4 KB | Display | PDB format |
PDBx/mmJSON format | 3efk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ef/3efk ftp://data.pdbj.org/pub/pdb/validation_reports/ef/3efk | HTTPS FTP |
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-Related structure data
Related structure data | 3efjC 1r1wS 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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2 |
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3 |
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Unit cell |
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-Components
#1: Protein | Mass: 35346.910 Da / Num. of mol.: 2 / Fragment: c-Met kinase domain, UNP residues 1048-1351 / Mutation: V1272L Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P08581, 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: 2.73 Å3/Da / Density % sol: 55.02 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion / pH: 5 Details: 12% PEG 6000, 1.0M LiCl2, 0.1M Sodium Citrate, pH 5.0, VAPOR DIFFUSION, temperature 298K |
-Data collection
Diffraction | Mean temperature: 130 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jul 30, 2004 / Details: osmic |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→19.64 Å / Num. all: 40217 / Num. obs: 39332 / % possible obs: 97.8 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Redundancy: 3.6 % / Rmerge(I) obs: 0.057 / Net I/σ(I): 20 |
Reflection shell | Resolution: 2.2→2.28 Å / Rmerge(I) obs: 0.422 / Mean I/σ(I) obs: 2.5 / Num. unique all: 3699 / % possible all: 93.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1r1w Resolution: 2.2→19.64 Å / Cor.coef. Fo:Fc: 0.923 / Cor.coef. Fo:Fc free: 0.907 / SU B: 6.712 / SU ML: 0.172 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / ESU R: 0.278 / ESU R Free: 0.228 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 38.372 Å2
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Refinement step | Cycle: LAST / Resolution: 2.2→19.64 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.2→2.257 Å / Total num. of bins used: 20
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