[English] 日本語
Yorodumi- PDB-4r6v: Crystal Structure of FGF Receptor (FGFR) 4 Kinase Harboring the V... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4r6v | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal Structure of FGF Receptor (FGFR) 4 Kinase Harboring the V550L Gate-Keeper Mutation in Complex with FIIN-3, an Irreversible Tyrosine Kinase Inhibitor Capable of Overcoming FGFR kinase Gate-Keeper Mutations | ||||||
Components | Fibroblast growth factor receptor 4 | ||||||
Keywords | Transferase/transferase inhibitor / Kinase Domain Fold / Cell Signaling / Phosphotransferase / Plasmamembrane / Transferase-transferase inhibitor complex | ||||||
Function / homology | Function and homology information FGFR4 mutant receptor activation / betaKlotho-mediated ligand binding / regulation of extracellular matrix disassembly / phosphate ion homeostasis / regulation of bile acid biosynthetic process / FGFR4 ligand binding and activation / fibroblast growth factor receptor activity / Phospholipase C-mediated cascade; FGFR4 / positive regulation of catalytic activity / positive regulation of DNA biosynthetic process ...FGFR4 mutant receptor activation / betaKlotho-mediated ligand binding / regulation of extracellular matrix disassembly / phosphate ion homeostasis / regulation of bile acid biosynthetic process / FGFR4 ligand binding and activation / fibroblast growth factor receptor activity / Phospholipase C-mediated cascade; FGFR4 / positive regulation of catalytic activity / positive regulation of DNA biosynthetic process / fibroblast growth factor binding / PI-3K cascade:FGFR4 / positive regulation of proteolysis / regulation of lipid metabolic process / PI3K Cascade / fibroblast growth factor receptor signaling pathway / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / transport vesicle / FRS-mediated FGFR4 signaling / cholesterol homeostasis / receptor protein-tyrosine kinase / Negative regulation of FGFR4 signaling / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / PIP3 activates AKT signaling / glucose homeostasis / cell migration / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / heparin binding / RAF/MAP kinase cascade / protein autophosphorylation / receptor complex / positive regulation of ERK1 and ERK2 cascade / endosome / positive regulation of cell population proliferation / positive regulation of gene expression / Golgi apparatus / endoplasmic reticulum / extracellular region / ATP binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.353 Å | ||||||
Authors | Huang, Z. / Mohammadi, M. | ||||||
Citation | Journal: Proc.Natl.Acad.Sci.USA / Year: 2014 Title: Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Authors: Tan, L. / Wang, J. / Tanizaki, J. / Huang, Z. / Aref, A.R. / Rusan, M. / Zhu, S.J. / Zhang, Y. / Ercan, D. / Liao, R.G. / Capelletti, M. / Zhou, W. / Hur, W. / Kim, N. / Sim, T. / Gaudet, S. ...Authors: Tan, L. / Wang, J. / Tanizaki, J. / Huang, Z. / Aref, A.R. / Rusan, M. / Zhu, S.J. / Zhang, Y. / Ercan, D. / Liao, R.G. / Capelletti, M. / Zhou, W. / Hur, W. / Kim, N. / Sim, T. / Gaudet, S. / Barbie, D.A. / Yeh, J.R. / Yun, C.H. / Hammerman, P.S. / Mohammadi, M. / Janne, P.A. / Gray, N.S. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4r6v.cif.gz | 71.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4r6v.ent.gz | 51.6 KB | Display | PDB format |
PDBx/mmJSON format | 4r6v.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4r6v_validation.pdf.gz | 781 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 4r6v_full_validation.pdf.gz | 787.4 KB | Display | |
Data in XML | 4r6v_validation.xml.gz | 13.2 KB | Display | |
Data in CIF | 4r6v_validation.cif.gz | 17.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r6/4r6v ftp://data.pdbj.org/pub/pdb/validation_reports/r6/4r6v | HTTPS FTP |
-Related structure data
Related structure data | 4qqcSC 4r5sC S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 36173.598 Da / Num. of mol.: 1 / Fragment: Tyrosine Kinase Domain of FGF receptor 4 / Mutation: R664E, V550L Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FGFR4, JTK2, TKF / Production host: Escherichia coli (E. coli) References: UniProt: P22455, receptor protein-tyrosine kinase | ||
---|---|---|---|
#2: Chemical | ChemComp-FI3 / | ||
#3: Chemical | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.59 Å3/Da / Density % sol: 52.48 % |
---|---|
Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 0.1 M HEPES, 1.0-1.2 M (NH4)2SO4, 10 mM Yitrium (III) Chloride hexahydrate, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 291K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: NSLS / Beamline: X4C / Wavelength: 0.97916 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MAR CCD 165 mm / Detector: CCD / Date: Jul 21, 2014 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Si 111 Channel / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97916 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.35→50 Å / Num. all: 14984 / Num. obs: 14984 / % possible obs: 99.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 2.9 % / Rmerge(I) obs: 0.078 / Rsym value: 0.078 / Net I/σ(I): 12.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 4QQC Resolution: 2.353→38.544 Å / SU ML: 0.29 / σ(F): 2.01 / Phase error: 22.47 / Stereochemistry target values: ML
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.353→38.544 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Origin x: -61.4228 Å / Origin y: 142.1326 Å / Origin z: 10.6781 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group | Selection details: all |