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Yorodumi- PDB-4xyf: Crystal structure of c-Met in complex with (S)-5-(8-fluoro-3-(1-(... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4xyf | ||||||
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Title | Crystal structure of c-Met in complex with (S)-5-(8-fluoro-3-(1-(3-(2-methoxyethoxy)quinolin-6-yl)ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-methylisoxazole | ||||||
Components | Hepatocyte growth factor receptorC-Met | ||||||
Keywords | TRANSFERASE/TRANSFERASE Inhibitor / receptor tyrosine kinase / inhibitor / complex / intracellular catalytic domain / TRANSFERASE-TRANSFERASE Inhibitor complex | ||||||
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: 1.85 Å | ||||||
Authors | Whittington, D.A. / Long, A.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Discovery of Potent and Selective 8-Fluorotriazolopyridine c-Met Inhibitors. Authors: Peterson, E.A. / Teffera, Y. / Albrecht, B.K. / Bauer, D. / Bellon, S.F. / Boezio, A. / Boezio, C. / Broome, M.A. / Choquette, D. / Copeland, K.W. / Dussault, I. / Lewis, R. / Lin, M.H. / ...Authors: Peterson, E.A. / Teffera, Y. / Albrecht, B.K. / Bauer, D. / Bellon, S.F. / Boezio, A. / Boezio, C. / Broome, M.A. / Choquette, D. / Copeland, K.W. / Dussault, I. / Lewis, R. / Lin, M.H. / Lohman, J. / Liu, J. / Potashman, M. / Rex, K. / Shimanovich, R. / Whittington, D.A. / Vaida, K.R. / Harmange, J.C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4xyf.cif.gz | 81.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4xyf.ent.gz | 57.9 KB | Display | PDB format |
PDBx/mmJSON format | 4xyf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xy/4xyf ftp://data.pdbj.org/pub/pdb/validation_reports/xy/4xyf | HTTPS FTP |
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-Related structure data
Related structure data | 4xmoSC 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: 35215.715 Da / Num. of mol.: 1 / Fragment: kinase domain (UNP residues 1048-1351) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P08581, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-44X / |
#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: 2.04 Å3/Da / Density % sol: 39.69 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.8 Details: 13% PEG 4000, 100 mM HEPES, 6% (v/v) isopropanol, 3% (v/v) ethanol, 40 mM beta-mercaptoethanol |
-Data collection
Diffraction | Mean temperature: 100 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: Mar 26, 2010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.85→50 Å / Num. all: 25556 / Num. obs: 20982 / % possible obs: 82.1 % / Observed criterion σ(I): -3 / Redundancy: 3.9 % / Biso Wilson estimate: 25.8 Å2 / Rmerge(I) obs: 0.054 / Χ2: 1.096 / Net I/av σ(I): 22.197 / Net I/σ(I): 19.6 / Num. measured all: 81489 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: 0
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4XMO Resolution: 1.85→40 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.935 / WRfactor Rfree: 0.2459 / WRfactor Rwork: 0.1939 / FOM work R set: 0.8369 / SU B: 3.331 / SU ML: 0.102 / SU R Cruickshank DPI: 0.1966 / SU Rfree: 0.172 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.197 / ESU R Free: 0.172 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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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: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 102.37 Å2 / Biso mean: 29 Å2 / Biso min: 13.44 Å2
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Refinement step | Cycle: final / Resolution: 1.85→40 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.85→1.898 Å / Total num. of bins used: 20
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