› 5wev

X-ray diffraction
1.85Å resolution

Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model

Released:
DOI: 10.2210/pdb5wev/pdb
PDB entry 5wev coloured by chain, front view.
PDB entry 5wev coloured by chain, side view.
PDB entry 5wev coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model.
Liang J, Van Abbema A, Balazs M, Barrett K, Berezhkovsky L, Blair WS, Chang C, Delarosa D, DeVoss J, Driscoll J, Eigenbrot C, Goodacre S, Ghilardi N, MacLeod C, Johnson A, Bir Kohli P, Lai Y, Lin Z, Mantik P, Menghrajani K, Nguyen H, Peng I, Sambrone A, Shia S, Smith J, Sohn S, Tsui V, Ultsch M, Williams K, Wu LC, Yang W, Zhang B, Magnuson S
Bioorg Med Chem Lett 27 4370-4376 (2017)
PMID: 28830649

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: 319 amino acids
Theoretical weight: 37.38 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: O60674 (Residues: 833-1132; Coverage: 27%)
Gene name: JAK2
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 9ZS 1 x 9ZS
1 modified residue:
Ligand PTR 2 x PTR

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: C2
Unit cell:
a: 107.653Å b: 69.542Å c: 50.629Å
α: 90° β: 98.93° γ: 90°
R-values:
R R work R free
0.167 0.166 0.194
Expression system: unidentified baculovirus

Quick links

Citations

2 review citations

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs.
Gadina et al. (2018)
1 more