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- PDB-5eyc: Crystal structure of c-Met in complex with naphthyridinone inhibitor 5 -
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Open data
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Basic information
Entry | Database: PDB / ID: 5eyc | ||||||
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Title | Crystal structure of c-Met in complex with naphthyridinone inhibitor 5 | ||||||
![]() | Hepatocyte growth factor receptor | ||||||
![]() | TRANSFERASE/TRANSFERASE INHIBITOR / phosphotransferase / inhibitor / cancer / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | ![]() negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor 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-plexin signaling pathway involved in axon guidance / semaphorin receptor activity ...negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor 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-plexin signaling pathway involved in axon guidance / semaphorin receptor activity / MET receptor recycling / semaphorin receptor complex / 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 / positive regulation of endothelial cell chemotaxis / 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 / neuron differentiation / Negative regulation of MET activity / receptor protein-tyrosine kinase / 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 / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Whittington, D.A. / Long, A.M. | ||||||
![]() | ![]() Title: Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective ...Title: Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity. Authors: Boezio, A.A. / Copeland, K.W. / Rex, K. / K Albrecht, B. / Bauer, D. / Bellon, S.F. / Boezio, C. / Broome, M.A. / Choquette, D. / Coxon, A. / Dussault, I. / Hirai, S. / Lewis, R. / Lin, M.H. ...Authors: Boezio, A.A. / Copeland, K.W. / Rex, K. / K Albrecht, B. / Bauer, D. / Bellon, S.F. / Boezio, C. / Broome, M.A. / Choquette, D. / Coxon, A. / Dussault, I. / Hirai, S. / Lewis, R. / Lin, M.H. / Lohman, J. / Liu, J. / Peterson, E.A. / Potashman, M. / Shimanovich, R. / Teffera, Y. / Whittington, D.A. / Vaida, K.R. / Harmange, J.C. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 80.8 KB | Display | ![]() |
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PDB format | ![]() | 58.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 759.9 KB | Display | ![]() |
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Full document | ![]() | 761.1 KB | Display | |
Data in XML | ![]() | 15.2 KB | Display | |
Data in CIF | ![]() | 22.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5eydC ![]() 4xmoS C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 35215.715 Da / Num. of mol.: 1 / Fragment: residues 1048-1351 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P08581, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-5SZ / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.04 Å3/Da / Density % sol: 39.77 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.8 Details: 12% PEG 4000, 3% (v/v) ethanol, 6% (v/v) isopropanol, 40 mM beta-mercaptoethanol, 100 mM HEPES (pH 7.8) |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jun 7, 2011 / Details: Varimax HR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.8→50 Å / Num. obs: 22824 / % possible obs: 82.4 % / Observed criterion σ(I): -3 / Redundancy: 2.9 % / Biso Wilson estimate: 28.99 Å2 / Rmerge(I) obs: 0.034 / Χ2: 1.083 / Net I/av σ(I): 20.341 / Net I/σ(I): 24.5 / Num. measured all: 65999 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4XMO Resolution: 1.8→41.74 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.937 / WRfactor Rfree: 0.267 / WRfactor Rwork: 0.2014 / FOM work R set: 0.8195 / SU B: 3.44 / SU ML: 0.106 / SU R Cruickshank DPI: 0.1796 / SU Rfree: 0.1671 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.18 / ESU R Free: 0.167 / 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: 113.16 Å2 / Biso mean: 31.058 Å2 / Biso min: 15.39 Å2
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Refinement step | Cycle: final / Resolution: 1.8→41.74 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.8→1.847 Å / Total num. of bins used: 20
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