+Open data
-Basic information
Entry | Database: PDB / ID: 8ow3 | ||||||
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Title | Crystal structure of wild-type c-MET bound by compound 2 | ||||||
Components | Hepatocyte growth factor receptorC-Met | ||||||
Keywords | TRANSFERASE / kinase / inhibitor / cancer research / drug discovery | ||||||
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 / basal plasma membrane / negative regulation of autophagy / 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 / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.27 Å | ||||||
Authors | Collie, G.W. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Discovery and Optimization of the First ATP Competitive Type-III c-MET Inhibitor. Authors: Michaelides, I.N. / Collie, G.W. / Borjesson, U. / Vasalou, C. / Alkhatib, O. / Barlind, L. / Cheung, T. / Dale, I.L. / Embrey, K.J. / Hennessy, E.J. / Khurana, P. / Koh, C.M. / Lamb, M.L. / ...Authors: Michaelides, I.N. / Collie, G.W. / Borjesson, U. / Vasalou, C. / Alkhatib, O. / Barlind, L. / Cheung, T. / Dale, I.L. / Embrey, K.J. / Hennessy, E.J. / Khurana, P. / Koh, C.M. / Lamb, M.L. / Liu, J. / Moss, T.A. / O'Neill, D.J. / Phillips, C. / Shaw, J. / Snijder, A. / Storer, R.I. / Stubbs, C.J. / Han, F. / Li, C. / Qiao, J. / Sun, D.Q. / Wang, J. / Wang, P. / Yang, W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ow3.cif.gz | 63.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ow3.ent.gz | 47 KB | Display | PDB format |
PDBx/mmJSON format | 8ow3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ow/8ow3 ftp://data.pdbj.org/pub/pdb/validation_reports/ow/8ow3 | HTTPS FTP |
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-Related structure data
Related structure data | 8ouuC 8ouvC 8ov7C 8ovzC 8owgC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 34842.320 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Production host: Escherichia coli (E. coli) References: UniProt: P08581, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-W40 / |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.07 Å3/Da / Density % sol: 40.46 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 12 % PEG3350, 5 % EtOH, 0.2 M Li2SO4, 100 mM PCPT pH 5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 2 / Wavelength: 0.98 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 5, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.27→46.4 Å / Num. obs: 13200 / % possible obs: 98.8 % / Redundancy: 3.4 % / CC1/2: 0.994 / Net I/σ(I): 6.4 |
Reflection shell | Resolution: 2.27→2.33 Å / Num. unique obs: 899 / CC1/2: 0.739 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.27→46.4 Å / Cor.coef. Fo:Fc: 0.871 / Cor.coef. Fo:Fc free: 0.819 / SU R Cruickshank DPI: 0.369 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.36 / SU Rfree Blow DPI: 0.263 / SU Rfree Cruickshank DPI: 0.268
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Displacement parameters | Biso mean: 47.66 Å2
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Refine analyze | Luzzati coordinate error obs: 0.39 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.27→46.4 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.27→2.3 Å
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