› 4ppa

X-ray diffraction
2.67Å resolution

ITK kinase domain with compound 11 (N-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)

Released:
DOI: 10.2210/pdb4ppa/pdb
PDB entry 4ppa coloured by chain, front view.
PDB entry 4ppa coloured by chain, side view.
PDB entry 4ppa coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors.
Pastor RM, Burch JD, Magnuson S, Ortwine DF, Chen Y, De La Torre K, Ding X, Eigenbrot C, Johnson A, Liimatta M, Liu Y, Shia S, Wang X, Wu LC, Pei Z
Bioorg Med Chem Lett 24 2448-52 (2014)
PMID: 24767842

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

Assemblies composition:
monomeric (preferred)
homo dimer
Assembly name:
PDBe Complex ID:
PDB-CPX-170703 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Tyrosine-protein kinase ITK/TSK Chains: A, B
Molecule details ›
Chains: A, B
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: Transferase(Phosphotransferase) domain 1

Ligands and Environments

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

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.1
Spacegroup: P212121
Unit cell:
a: 40.595Å b: 94.153Å c: 156.321Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.237 0.235 0.278
Expression system: Spodoptera frugiperda

Quick links

Citations

3 review citations

Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011-2020): Current Status and Future Prospects.
El-Gamal et al. (2022)
2 more

1 mention without citation

Trypsin specificity as elucidated by LIE calculations, X-ray structures, and association constant measurements.
Leiros et al. (2004)