[English] 日本語
Yorodumi- PDB-4aoi: Crystal structure of C-MET kinase domain in complex with 4-(3-((1... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4aoi | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of C-MET kinase domain in complex with 4-(3-((1H- pyrrolo(2,3-b)pyridin-3-yl)methyl)-(1,2,4)triazolo(4,3-b)(1,2,4) triazin-6-yl)benzonitrile | ||||||
Components | HEPATOCYTE GROWTH FACTOR RECEPTOR | ||||||
Keywords | TRANSFERASE / KINASE INHIBITOR | ||||||
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 / MET receptor recycling ...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 / MET receptor recycling / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / 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 / basal plasma membrane / MECP2 regulates neuronal receptors and channels / positive regulation of microtubule polymerization / negative regulation of autophagy / InlB-mediated entry of Listeria monocytogenes into host cell / excitatory postsynaptic potential / liver development / molecular function activator activity / receptor protein-tyrosine kinase / Negative regulation of MET activity / neuron differentiation / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / cell migration / nervous system development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / postsynapse / receptor complex / cell surface receptor signaling pathway / 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: 1.9 Å | ||||||
Authors | McTigue, M. / Grodsky, N. / Ryan, K. / Cui, J.J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Discovery of a Novel Class of Exquisitely Selective Mesenchymal-Epithelial Transition Factor (C-met) Protein Kinase Inhibitors and Identification of the Clinical Candidate 2-(4-(1-(Quinolin-6- ...Title: Discovery of a Novel Class of Exquisitely Selective Mesenchymal-Epithelial Transition Factor (C-met) Protein Kinase Inhibitors and Identification of the Clinical Candidate 2-(4-(1-(Quinolin-6-Ylmethyl)-1H-[1,2, 3]Triazolo[4,5-B]Pyrazin-6-Yl)-1H-Pyrazol-1-Yl)Ethanol (Pf-04217903) for the Treatment of Cancer. Authors: Cui, J.J. / Mctigue, M. / Nambu, M. / Tran-Dube, M. / Pairish, M. / Shen, H. / Jia, L. / Cheng, H. / Hoffman, J. / Le, P. / Jalaie, M. / Goetz, G.H. / Ryan, K. / Grodsky, N. / Deng, Y. / ...Authors: Cui, J.J. / Mctigue, M. / Nambu, M. / Tran-Dube, M. / Pairish, M. / Shen, H. / Jia, L. / Cheng, H. / Hoffman, J. / Le, P. / Jalaie, M. / Goetz, G.H. / Ryan, K. / Grodsky, N. / Deng, Y. / Parker, M. / Timofeevski, S. / Murray, B.W. / Yamazaki, S. / Aguirre, S. / Li, Q. / Zou, H. / Christensen, J. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4aoi.cif.gz | 82.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4aoi.ent.gz | 60.4 KB | Display | PDB format |
PDBx/mmJSON format | 4aoi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4aoi_validation.pdf.gz | 714 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 4aoi_full_validation.pdf.gz | 716.4 KB | Display | |
Data in XML | 4aoi_validation.xml.gz | 16.8 KB | Display | |
Data in CIF | 4aoi_validation.cif.gz | 25.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ao/4aoi ftp://data.pdbj.org/pub/pdb/validation_reports/ao/4aoi | HTTPS FTP |
-Related structure data
Related structure data | 3zxzC 3zzeC 4ap7C 2wkmS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 34879.414 Da / Num. of mol.: 1 / Fragment: TYROSINE KINASE DOMAIN, RESIDUES 1051-1348 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC1 / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) References: UniProt: P08581, receptor protein-tyrosine kinase |
---|---|
#2: Chemical | ChemComp-4K0 / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.4 Å3/Da / Density % sol: 48.7 % / Description: NONE |
---|---|
Crystal grow | Temperature: 286 K / Method: vapor diffusion, hanging drop Details: CRYSTALS WERE OBTAINED AT 13 DEGREES CELCIUS FROM HANGING DROPS CONTAINING 1.2 MICROLITERS OF PROTEIN: COMPOUND SOLUTION (1:5 MOLAR RATIO) AND 1.2 MICROLITERS OF PRECIPITATING SOLUTION (0.05 ...Details: CRYSTALS WERE OBTAINED AT 13 DEGREES CELCIUS FROM HANGING DROPS CONTAINING 1.2 MICROLITERS OF PROTEIN: COMPOUND SOLUTION (1:5 MOLAR RATIO) AND 1.2 MICROLITERS OF PRECIPITATING SOLUTION (0.05 M CITRATE-PHOSPHATE, PH 4.6, 0-25 MM NACL, 21 % (W/V) PEG-3350). TO OBTAIN LARGER CRYSTALS, STREAK SEEDING WAS EMPLOYED USING THE CRYSTALS JUST MENTIONED AS DONORS, UNDER THE SAME CONDITIONS EXCEPT 275 MM NACL WAS USED AND THE DROPS WERE EQUILIBRATED OVERNIGHT BEFORE SEEDING WAS PERFORMED. |
-Data collection
Diffraction | Mean temperature: 96 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Mar 9, 2006 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→50 Å / Num. obs: 26935 / % possible obs: 99.3 % / Observed criterion σ(I): 2 / Redundancy: 3.6 % / Biso Wilson estimate: 10 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 22 |
Reflection shell | Resolution: 1.9→1.94 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.3 / Mean I/σ(I) obs: 3.9 / % possible all: 98 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2WKM Resolution: 1.9→41.61 Å / Rfactor Rfree error: 0.008 / Data cutoff high absF: 43518.05 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Solvent model: FLAT MODEL / Bsol: 70.2907 Å2 / ksol: 0.371167 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.1 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→41.61 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.8→1.91 Å / Rfactor Rfree error: 0.069 / Total num. of bins used: 6
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Xplor file |
|