+Open data
-Basic information
Entry | Database: PDB / ID: 8kh8 | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of FGFR4(V550L) kinase domain with 8z | ||||||
Components | Fibroblast growth factor receptor 4 | ||||||
Keywords | TRANSFERASE/INHIBITOR / FGFR4 kinase domain / 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 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 | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.49 Å | ||||||
Authors | Lin, Q.M. / Chen, X.J. / Chen, Y.H. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: J.Med.Chem. / Year: 2024 Title: Discovery of 6-Formylpyridyl Urea Derivatives as Potent Reversible-Covalent Fibroblast Growth Factor Receptor 4 Inhibitors with Improved Anti-Hepatocellular Carcinoma Activity. Authors: Yang, F. / Lin, Q. / Song, X. / Huang, H. / Chen, X. / Tan, J. / Li, Y. / Zhou, Y. / Tu, Z. / Du, H. / Zhang, Z.M. / Ortega, R. / Lin, X. / Patterson, A.V. / Smaill, J.B. / Chen, Y. / Lu, X. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8kh8.cif.gz | 84.4 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8kh8.ent.gz | 59.8 KB | Display | PDB format |
PDBx/mmJSON format | 8kh8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8kh8_validation.pdf.gz | 773.3 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8kh8_full_validation.pdf.gz | 778.6 KB | Display | |
Data in XML | 8kh8_validation.xml.gz | 17.3 KB | Display | |
Data in CIF | 8kh8_validation.cif.gz | 26.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kh/8kh8 ftp://data.pdbj.org/pub/pdb/validation_reports/kh/8kh8 | HTTPS FTP |
-Related structure data
Related structure data | 8kh6C 8kh7C 8kh9C 8w5cC 7wcwS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 34522.855 Da / Num. of mol.: 1 / Mutation: C477A,V550L,R664E 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-SO4 / |
#3: Chemical | ChemComp-VVW / Mass: 712.583 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C32H35Cl2N9O6 / Feature type: SUBJECT OF INVESTIGATION |
#4: Chemical | ChemComp-EDO / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.25 Å3/Da / Density % sol: 45.21 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 0.1 M Bis-Tris (pH 4.5), 0.2 M Li2SO4, 16-19% PEG3350 |
-Data collection
Diffraction | Mean temperature: 277 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.9792 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 20, 2023 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9792 Å / Relative weight: 1 |
Reflection | Resolution: 1.49→61.46 Å / Num. obs: 49894 / % possible obs: 99.9 % / Redundancy: 6.3 % / CC1/2: 0.993 / Net I/σ(I): 7.8 |
Reflection shell | Resolution: 1.49→1.53 Å / Num. unique obs: 3623 / CC1/2: 0.43 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7WCW Resolution: 1.49→36.66 Å / SU ML: 0.15 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 19.92 / 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: 1.49→36.66 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|