› 4pgz

X-ray diffraction
2.4Å resolution

Structural basis of KIT activation by oncogenic mutations in the extracellular region reveals a zipper-like mechanism for ligand-dependent or oncogenic receptor tyrosine kinase activation

Released:
DOI: 10.2210/pdb4pgz/pdb
PDB entry 4pgz coloured by chain, front view.
PDB entry 4pgz coloured by chain, side view.
PDB entry 4pgz coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
The strength and cooperativity of KIT ectodomain contacts determine normal ligand-dependent stimulation or oncogenic activation in cancer.
Reshetnyak AV, Opatowsky Y, Boggon TJ, Folta-Stogniew E, Tome F, Lax I, Schlessinger J
Mol Cell 57 191-201 (2015)
PMID: 25544564

Function and Biology Details

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

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-145430 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Mast/stem cell growth factor receptor Kit Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 208 amino acids
Theoretical weight: 23.36 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P10721 (Residues: 308-518; Coverage: 22%)
Gene names: KIT, SCFR
Structure domains: Immunoglobulins

Ligands and Environments

2 bound ligands:
Ligand NAG 3 x NAG
Ligand CO 5 x CO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: C2
Unit cell:
a: 163.592Å b: 63.548Å c: 81.547Å
α: 90° β: 117.46° γ: 90°
R-values:
R R work R free
0.233 0.232 0.262
Expression system: Spodoptera frugiperda

Quick links

Citations

6 review citations

Translational insights into gastrointestinal stromal tumor and current clinical advances.
Hemming et al. (2018)
5 more

1 mention without citation

Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention.
Krimmer et al. (2023)