+Open data
-Basic information
Entry | Database: PDB / ID: 7y4t | ||||||
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Title | Crystal structure of cMET kinase domain bound by compound 9I | ||||||
Components | Hepatocyte growth factor receptorC-Met | ||||||
Keywords | TRANSFERASE/INHIBITOR / TRANSFERASE INHIBITOR / 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 / 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: 2.16 Å | ||||||
Authors | Qu, L.Z. / Chen, Y.H. | ||||||
Funding support | China, 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: Discovery of D6808, a Highly Selective and Potent Macrocyclic c-Met Inhibitor for Gastric Cancer Harboring MET Gene Alteration Treatment. Authors: Wang, C. / Li, J. / Qu, L. / Tang, X. / Song, X. / Yang, F. / Chen, X. / Lin, Q. / Lin, W. / Zhou, Y. / Tu, Z. / Chen, Y. / Zhang, Z. / Lu, X. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7y4t.cif.gz | 131.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7y4t.ent.gz | 98.7 KB | Display | PDB format |
PDBx/mmJSON format | 7y4t.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y4/7y4t ftp://data.pdbj.org/pub/pdb/validation_reports/y4/7y4t | HTTPS FTP |
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-Related structure data
Related structure data | 7y4uC 8gvjC 6sd9S S: Starting model for refinement 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 / Fragment: kinase domain 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-I90 / |
#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: 2.97 Å3/Da / Density % sol: 58.58 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / Details: 0.1 M HEPES (pH 7.8), 15-30% (v/v) PEG 8000 / PH range: 7.8 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.97915 Å |
Detector | Type: ADSC QUANTUM 1 / Detector: CCD / Date: Oct 18, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97915 Å / Relative weight: 1 |
Reflection | Resolution: 2.16→29.5 Å / Num. obs: 23530 / % possible obs: 100 % / Redundancy: 22.4 % / CC1/2: 1 / Net I/σ(I): 23.16 |
Reflection shell | Resolution: 2.16→2.3 Å / Num. unique obs: 2293 / CC1/2: 0.884 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6SD9 Resolution: 2.16→29.5 Å / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 24.98 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 122.11 Å2 / Biso mean: 56.1684 Å2 / Biso min: 32.4 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.16→29.5 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 9 / % reflection obs: 100 %
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Refinement TLS params. | Method: refined / Origin x: -16.997 Å / Origin y: 5.3755 Å / Origin z: -21.3408 Å
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Refinement TLS group | Selection details: all |