› 4p7e

X-ray diffraction
2.4Å resolution

Triazolopyridine compounds as selective JAK1 inhibitors: from hit identification to GLPG0634

Released:
DOI: 10.2210/pdb4p7e/pdb
PDB entry 4p7e coloured by chain, front view.
PDB entry 4p7e coloured by chain, side view.
PDB entry 4p7e coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634.
Menet CJ, Fletcher SR, Van Lommen G, Geney R, Blanc J, Smits K, Jouannigot N, Deprez P, van der Aar EM, Clement-Lacroix P, Lepescheux L, Galien R, Vayssiere B, Nelles L, Christophe T, Brys R, Uhring M, Ciesielski F, Van Rompaey L
J Med Chem 57 9323-42 (2014)
PMID: 25369270

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-130063 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Tyrosine-protein kinase JAK2 Chains: A, B
Molecule details ›
Chains: A, B
Length: 293 amino acids
Theoretical weight: 34.59 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O60674 (Residues: 840-1132; Coverage: 26%)
Gene name: JAK2
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 2HB 2 x 2HB
1 modified residue:
Ligand PTR 4 x PTR

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P41
Unit cell:
a: 111.39Å b: 111.39Å c: 71.08Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.208 0.205 0.267
Expression system: Spodoptera frugiperda

Quick links

Citations

12 review citations

JAK inhibition as a therapeutic strategy for immune and inflammatory diseases.
Schwartz et al. (2017)
11 more

4 mentions without citation

A Comprehensive Overview of Globally Approved JAK Inhibitors.
Shawky et al. (2022)
3 more