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Yorodumi- PDB-3u6i: Crystal structure of c-Met in complex with pyrazolone inhibitor 58a -
+Open data
-Basic information
Entry | Database: PDB / ID: 3u6i | ||||||
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Title | Crystal structure of c-Met in complex with pyrazolone inhibitor 58a | ||||||
Components | Hepatocyte growth factor receptorC-Met | ||||||
Keywords | transferase/transferase inhibitor / kinase domain / phosphotransferase / cancer / hepatocyte growth factor / 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: 2.1 Å | ||||||
Authors | Bellon, S.F. / Whittington, D.A. / Long, A.L. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Structure-based design of novel class II c-Met inhibitors: 1. Identification of pyrazolone-based derivatives. Authors: Norman, M.H. / Liu, L. / Lee, M. / Xi, N. / Fellows, I. / D'Angelo, N.D. / Dominguez, C. / Rex, K. / Bellon, S.F. / Kim, T.S. / Dussault, I. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3u6i.cif.gz | 80.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3u6i.ent.gz | 57.5 KB | Display | PDB format |
PDBx/mmJSON format | 3u6i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u6/3u6i ftp://data.pdbj.org/pub/pdb/validation_reports/u6/3u6i | HTTPS FTP |
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-Related structure data
Related structure data | 3u6hC 3u6jC 2rfnS 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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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 35215.715 Da / Num. of mol.: 1 / Fragment: unp residues 1048-1315 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Plasmid: pFastBac1 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P08581, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-044 / |
#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: 2.67 Å3/Da / Density % sol: 53.86 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 5 Details: 12% PEG 6000, 1.0 M lithium chloride, 0.1 M sodium citrate, pH 5.0, VAPOR DIFFUSION, temperature 293K |
-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: Sep 19, 2005 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.1→50 Å / Num. obs: 21582 / % possible obs: 97.2 % / Observed criterion σ(I): -3 / Redundancy: 3.3 % / Rmerge(I) obs: 0.052 / Χ2: 1.543 / Net I/σ(I): 28.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 2RFN Resolution: 2.1→50 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.912 / WRfactor Rfree: 0.2657 / WRfactor Rwork: 0.21 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.825 / SU B: 5.074 / SU ML: 0.138 / SU R Cruickshank DPI: 0.2278 / SU Rfree: 0.1989 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.199 / 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 max: 64.53 Å2 / Biso mean: 30.7897 Å2 / Biso min: 7.85 Å2
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Refinement step | Cycle: LAST / Resolution: 2.1→50 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.104→2.158 Å / Total num. of bins used: 20
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