› 4r6v

X-ray diffraction
2.35Å resolution

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

Released:
DOI: 10.2210/pdb4r6v/pdb
PDB entry 4r6v coloured by chain, front view.
PDB entry 4r6v coloured by chain, side view.
PDB entry 4r6v coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors.
Tan L, Wang J, Tanizaki J, Huang Z, Aref AR, Rusan M, Zhu SJ, Zhang Y, Ercan D, Liao RG, Capelletti M, Zhou W, Hur W, Kim N, Sim T, Gaudet S, Barbie DA, Yeh JR, Yun CH, Hammerman PS, Mohammadi M, Jänne PA, Gray NS
Proc Natl Acad Sci U S A 111 E4869-77 (2014)
PMID: 25349422

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-149636 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Fibroblast growth factor receptor 4 Chain: A
Molecule details ›
Chain: A
Length: 323 amino acids
Theoretical weight: 36.17 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P22455 (Residues: 445-753; Coverage: 40%)
Gene names: FGFR4, JTK2, TKF
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand FI3 1 x FI3
Ligand SO4 2 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X4C
Spacegroup: R3
Unit cell:
a: 139.381Å b: 139.381Å c: 50.09Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.18 0.174 0.227
Expression system: Escherichia coli

Quick links

Citations

41 review citations

Advances and challenges in targeting FGFR signalling in cancer.
Babina et al. (2017)
40 more

6 mentions without citation

Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors.
Dai et al. (2019)
5 more