› 6xvb

X-ray diffraction
2.15Å resolution

Crystal structure of the kinase domain of human c-KIT with a cyclic imidate inhibitor covalently bound to Cys788

Released:
DOI: 10.2210/pdb6xvb/pdb
PDB entry 6xvb coloured by chain, front view.
PDB entry 6xvb coloured by chain, side view.
PDB entry 6xvb coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Alkynyl Benzoxazines and Dihydroquinazolines as Cysteine Targeting Covalent Warheads and Their Application in Identification of Selective Irreversible Kinase Inhibitors.
McAulay K, Hoyt EA, Thomas M, Schimpl M, Bodnarchuk MS, Lewis HJ, Barratt D, Bhavsar D, Robinson DM, Deery MJ, Ogg DJ, Bernardes GJL, Ward RA, Waring MJ, Kettle JG
J Am Chem Soc 142 10358-10372 (2020)
PMID: 32412754

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-145426 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Mast/stem cell growth factor receptor Kit Chains: A, B
Molecule details ›
Chains: A, B
Length: 328 amino acids
Theoretical weight: 37.33 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P10721 (Residues: 551-687, 766-934; Coverage: 32%)
Gene names: KIT, SCFR
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

1 bound ligand:
Ligand O2H 2 x O2H
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I03
Spacegroup: P212121
Unit cell:
a: 87.71Å b: 90.272Å c: 91.178Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.194 0.192 0.223
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

3 review citations

Covalent Warheads Targeting Cysteine Residue: The Promising Approach in Drug Development.
Huang et al. (2022)
2 more

4 mentions without citation

Recent advances in the development of covalent inhibitors.
Kim et al. (2021)
3 more