› 6tpd

X-ray diffraction
1.99Å resolution

Fragment-based discovery of pyrazolopyridones as JAK1 inhibitors with excellent subtype selectivity

Released:
DOI: 10.2210/pdb6tpd/pdb
PDB entry 6tpd coloured by chain, front view.
PDB entry 6tpd coloured by chain, side view.
PDB entry 6tpd coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Fragment-Based Discovery of Pyrazolopyridones as JAK1 Inhibitors with Excellent Subtype Selectivity.
Hansen BB, Jepsen TH, Larsen M, Sindet R, Vifian T, Burhardt MN, Larsen J, Seitzberg JG, Carnerup MA, Jerre A, Mølck C, Lovato P, Rai S, Nasipireddy VR, Ritzén A
J Med Chem 63 7008-7032 (2020)
PMID: 32462873

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 Chain: A
Molecule details ›
Chain: A
Length: 289 amino acids
Theoretical weight: 33.96 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O60674 (Residues: 842-1130; Coverage: 26%)
Gene name: JAK2
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

1 bound ligand:
Ligand QZ8 1 x QZ8
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I02
Spacegroup: C2
Unit cell:
a: 107.411Å b: 69.669Å c: 50.798Å
α: 90° β: 98.45° γ: 90°
R-values:
R R work R free
0.226 0.223 0.278
Expression system: Spodoptera frugiperda

Quick links

Citations

3 review citations

Fragment-to-Lead Medicinal Chemistry Publications in 2020.
de Esch et al. (2022)
2 more