+Open data
-Basic information
Entry | Database: PDB / ID: 6sde | ||||||
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Title | Crystal structure of wild-type cMET bound by savolitinib | ||||||
Components | Hepatocyte growth factor receptor | ||||||
Keywords | TRANSFERASE / Kinase / inhibitor | ||||||
Function / homology | Function and homology information 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 | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.49 Å | ||||||
Authors | Collie, G.W. / Phillips, C. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2019 Title: Structural and Molecular Insight into Resistance Mechanisms of First Generation cMET Inhibitors. Authors: Collie, G.W. / Koh, C.M. / O'Neill, D.J. / Stubbs, C.J. / Khurana, P. / Eddershaw, A. / Snijder, A. / Mauritzson, F. / Barlind, L. / Dale, I.L. / Shaw, J. / Phillips, C. / Hennessy, E.J. / ...Authors: Collie, G.W. / Koh, C.M. / O'Neill, D.J. / Stubbs, C.J. / Khurana, P. / Eddershaw, A. / Snijder, A. / Mauritzson, F. / Barlind, L. / Dale, I.L. / Shaw, J. / Phillips, C. / Hennessy, E.J. / Cheung, T. / Narvaez, A.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6sde.cif.gz | 124.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6sde.ent.gz | 96 KB | Display | PDB format |
PDBx/mmJSON format | 6sde.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6sde_validation.pdf.gz | 706.7 KB | Display | wwPDB validaton report |
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Full document | 6sde_full_validation.pdf.gz | 707.6 KB | Display | |
Data in XML | 6sde_validation.xml.gz | 12 KB | Display | |
Data in CIF | 6sde_validation.cif.gz | 16.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sd/6sde ftp://data.pdbj.org/pub/pdb/validation_reports/sd/6sde | HTTPS FTP |
-Related structure data
Related structure data | 6sd9C 6sdcC 6sddC 2wgjS 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: 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-V0L / |
#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: 2.34 Å3/Da / Density % sol: 47.34 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 15 % 2-propanol, 15 % PEG4K, 0.2 M PCPT pH 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.98003 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Jul 13, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98003 Å / Relative weight: 1 |
Reflection | Resolution: 2.49→43.36 Å / Num. obs: 10493 / % possible obs: 99.1 % / Redundancy: 6.5 % / CC1/2: 0.997 / Net I/σ(I): 8.8 |
Reflection shell | Resolution: 2.49→2.56 Å / Num. unique obs: 718 / CC1/2: 0.427 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2WGJ Resolution: 2.49→41.78 Å / Cor.coef. Fo:Fc: 0.931 / Cor.coef. Fo:Fc free: 0.849 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.598 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.721 / SU Rfree Blow DPI: 0.317 / SU Rfree Cruickshank DPI: 0.314
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Displacement parameters | Biso max: 161 Å2 / Biso mean: 69.55 Å2 / Biso min: 34.86 Å2
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Refine analyze | Luzzati coordinate error obs: 0.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.49→41.78 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.49→2.78 Å / Rfactor Rfree error: 0 / Total num. of bins used: 5
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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