[English] 日本語
Yorodumi- PDB-6iuo: Crystal structure of FGFR4 kinase domain in complex with a covale... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6iuo | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of FGFR4 kinase domain in complex with a covalent inhibitor | ||||||
Components | Fibroblast growth factor receptor 4 | ||||||
Keywords | TRANSFERASE/INHIBITOR / protein kinase / TRANSFERASE-INHIBITOR complex | ||||||
Function / homology | Function and homology information FGFR4 mutant receptor activation / betaKlotho-mediated ligand binding / regulation of extracellular matrix disassembly / fibroblast growth factor receptor activity / phosphate ion homeostasis / regulation of bile acid biosynthetic process / FGFR4 ligand binding and activation / 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 / fibroblast growth factor receptor activity / phosphate ion homeostasis / regulation of bile acid biosynthetic process / FGFR4 ligand binding and activation / 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 / FRS-mediated FGFR4 signaling / transport vesicle / cholesterol homeostasis / Negative regulation of FGFR4 signaling / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / PIP3 activates AKT signaling / glucose homeostasis / heparin binding / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein autophosphorylation / positive regulation of ERK1 and ERK2 cascade / receptor complex / 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 / molecular replacement / Resolution: 2.3 Å | ||||||
Authors | Xu, Y. / Liu, Q. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Discovery and Development of a Series of Pyrazolo[3,4-d]pyridazinone Compounds as the Novel Covalent Fibroblast Growth Factor Receptor Inhibitors by the Rational Drug Design. Authors: Wang, Y. / Dai, Y. / Wu, X. / Li, F. / Liu, B. / Li, C. / Liu, Q. / Zhou, Y. / Wang, B. / Zhu, M. / Cui, R. / Tan, X. / Xiong, Z. / Liu, J. / Tan, M. / Xu, Y. / Geng, M. / Jiang, H. / Liu, H. ...Authors: Wang, Y. / Dai, Y. / Wu, X. / Li, F. / Liu, B. / Li, C. / Liu, Q. / Zhou, Y. / Wang, B. / Zhu, M. / Cui, R. / Tan, X. / Xiong, Z. / Liu, J. / Tan, M. / Xu, Y. / Geng, M. / Jiang, H. / Liu, H. / Ai, J. / Zheng, M. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6iuo.cif.gz | 70.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6iuo.ent.gz | 49.5 KB | Display | PDB format |
PDBx/mmJSON format | 6iuo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6iuo_validation.pdf.gz | 794.5 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6iuo_full_validation.pdf.gz | 796 KB | Display | |
Data in XML | 6iuo_validation.xml.gz | 12.7 KB | Display | |
Data in CIF | 6iuo_validation.cif.gz | 16.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/iu/6iuo ftp://data.pdbj.org/pub/pdb/validation_reports/iu/6iuo | HTTPS FTP |
-Related structure data
Related structure data | 6itjC 6iupC 4qqtS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 35963.375 Da / Num. of mol.: 1 / Fragment: UNP residues 445-753 / Mutation: R664E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FGFR4 / Production host: Escherichia coli (E. coli) References: UniProt: P22455, receptor protein-tyrosine kinase |
---|---|
#2: Chemical | ChemComp-AWX / |
#3: Water | ChemComp-HOH / |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.66 Å3/Da / Density % sol: 53.81 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 0.1M HEPES pH7.5, 1.3 M (NH4)2SO4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.979 Å |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 14, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→50 Å / Num. obs: 15826 / % possible obs: 99.5 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.113 / Net I/σ(I): 4.8 |
Reflection shell | Resolution: 2.3→2.38 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.788 / % possible all: 98.8 |
-Phasing
Phasing | Method: molecular replacement | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Phasing MR |
|
-Processing
Software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4QQT Resolution: 2.3→50 Å / SU B: 7.558 / SU ML: 0.176 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.287 / ESU R Free: 0.219 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING
| ||||||||||||||||||||||||
Displacement parameters | Biso mean: 36.63 Å2
| ||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.3→50 Å
|