[English] 日本語
![](img/lk-miru.gif)
- PDB-8xlq: FGFR4 kinase domain with a dual-warhead covalent inhibitor CXF-007 -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 8xlq | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | FGFR4 kinase domain with a dual-warhead covalent inhibitor CXF-007 | |||||||||
![]() | Fibroblast growth factor receptor 4 | |||||||||
![]() | TRANSFERASE/INHIBITOR / Fibroblast growth factor receptor 4 / TRANSFERASE / TRANSFERASE-INHIBITOR complex | |||||||||
Function / homology | ![]() 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 DNA biosynthetic process / positive regulation of catalytic activity ...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 DNA biosynthetic process / positive regulation of catalytic activity / 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 / 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 | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Chen, X.J. / Chen, Y.H. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Design, synthesis, and biological evaluation of selective covalent inhibitors of FGFR4. Authors: Chen, X. / Li, H. / Lin, Q. / Dai, S. / Qu, L. / Guo, M. / Zhang, L. / Liao, J. / Wei, H. / Xu, G. / Jiang, L. / Chen, Y. | |||||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 81.1 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 784.3 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 787.8 KB | Display | |
Data in XML | ![]() | 15.6 KB | Display | |
Data in CIF | ![]() | 22.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8xloC ![]() 7v29S S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-
Components
#1: Protein | Mass: 34695.059 Da / Num. of mol.: 1 / Fragment: kinase domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P22455, receptor protein-tyrosine kinase | ||||
---|---|---|---|---|---|
#2: Chemical | ChemComp-A1LVQ / Mass: 619.670 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H33N7O5 / Feature type: SUBJECT OF INVESTIGATION | ||||
#3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 2.23 Å3/Da / Density % sol: 44.84 % |
---|---|
Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, hanging drop Details: 0.1 M Bis-Tris (pH 4.5), 0.2 M Li2SO4, 16-20% PEG3350 |
-Data collection
Diffraction | Mean temperature: 80 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 24, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→60.47 Å / Num. obs: 22227 / % possible obs: 99.24 % / Redundancy: 6.3 % / Biso Wilson estimate: 27.73 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.08815 / Net I/σ(I): 14.1 |
Reflection shell | Resolution: 1.95→2.02 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.554 / Mean I/σ(I) obs: 2.47 / Num. unique obs: 2210 / CC1/2: 0.876 / % possible all: 97.91 |
-
Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: 7V29 Resolution: 1.95→60.468 Å / SU ML: 0.21 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 25.53 / Stereochemistry target values: ML
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 103.93 Å2 / Biso mean: 36.4847 Å2 / Biso min: 16.29 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.95→60.468 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
|