› 4kio

X-ray diffraction
2.18Å resolution

Kinase domain mutant of human Itk in complex with a covalently-binding inhibitor

Released:
DOI: 10.2210/pdb4kio/pdb
PDB entry 4kio coloured by chain, front view.
PDB entry 4kio coloured by chain, side view.
PDB entry 4kio coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of novel irreversible inhibitors of interleukin (IL)-2-inducible tyrosine kinase (Itk) by targeting cysteine 442 in the ATP pocket.
Harling JD, Deakin AM, Campos S, Grimley R, Chaudry L, Nye C, Polyakova O, Bessant CM, Barton N, Somers D, Barrett J, Graves RH, Hanns L, Kerr WJ, Solari R
J Biol Chem 288 28195-206 (2013)
PMID: 23935099

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-170703 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Tyrosine-protein kinase ITK/TSK Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 266 amino acids
Theoretical weight: 30.21 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q08881 (Residues: 357-620; Coverage: 43%)
Gene names: EMT, ITK, LYK
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

4 bound ligands:
Ligand G5K 3 x G5K
Ligand G6K 2 x G6K
Ligand SO4 4 x SO4
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I03
Spacegroup: P21
Unit cell:
a: 69.309Å b: 69.279Å c: 141.852Å
α: 90° β: 100.87° γ: 90°
R-values:
R R work R free
0.167 0.165 0.202
Expression system: Spodoptera frugiperda

Quick links

Citations

2 review citations

Target engagement in lead generation.
Durham et al. (2015)
1 more

2 mentions without citation

Discovery of novel irreversible inhibitors of interleukin (IL)-2-inducible tyrosine kinase (Itk) by targeting cysteine 442 in the ATP pocket.
Harling et al. (2013)
1 more