› 4rfm

X-ray diffraction
2.1Å resolution

ITK kinase domain in complex with compound 1 N-{1-[(1,1-dioxo-1-thian-2-yl)(phenyl)methyl]-1H- pyrazol-4-yl}-5,5-difluoro-5a-methyl-1H,4H,4aH,5H,5aH,6H-cyclopropa[f]indazole-3-carboxamide

Released:
DOI: 10.2210/pdb4rfm/pdb
PDB entry 4rfm coloured by chain, front view.
PDB entry 4rfm coloured by chain, side view.
PDB entry 4rfm coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Tetrahydroindazoles as Interleukin-2 Inducible T-Cell Kinase Inhibitors. Part II. Second-Generation Analogues with Enhanced Potency, Selectivity, and Pharmacodynamic Modulation in Vivo.
Burch JD, Barrett K, Chen Y, DeVoss J, Eigenbrot C, Goldsmith R, Ismaili MH, Lau K, Lin Z, Ortwine DF, Zarrin AA, McEwan PA, Barker JJ, Ellebrandt C, Kordt D, Stein DB, Wang X, Chen Y, Hu B, Xu X, Yuen PW, Zhang Y, Pei Z
J Med Chem 58 3806-16 (2015)
PMID: 25844760

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 Chain: A
Molecule details ›
Chain: A
Length: 266 amino acids
Theoretical weight: 30.12 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

1 bound ligand:
Ligand 3P6 1 x 3P6
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007 HF
Spacegroup: P21
Unit cell:
a: 40.006Å b: 69.561Å c: 47.347Å
α: 90° β: 113.39° γ: 90°
R-values:
R R work R free
0.206 0.203 0.264
Expression system: Spodoptera frugiperda

Quick links

Citations

2 review citations

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

4 mentions without citation

EMBER-Embedding Multiple Molecular Fingerprints for Virtual Screening.
Mendolia et al. (2022)
3 more