› 5tkd

X-ray diffraction
1.92Å resolution

CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH 6-[(3,5-DIMETHYLPHE NYL)AMINO]-8- (METHYLAMINO)IMIDAZO[1,2-B]PYRIDAZINE-3-CARBO XAMIDE

Released:
DOI: 10.2210/pdb5tkd/pdb
PDB entry 5tkd coloured by chain, front view.
PDB entry 5tkd coloured by chain, side view.
PDB entry 5tkd coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of imidazo[1,2-b]pyridazine TYK2 pseudokinase ligands as potent and selective allosteric inhibitors of TYK2 signalling.
Moslin R, Gardner D, Santella J, Zhang Y, Duncia JV, Liu C, Lin J, Tokarski JS, Strnad J, Pedicord D, Chen J, Blat Y, Zupa-Fernandez A, Cheng L, Sun H, Chaudhry C, Huang C, D'Arienzo C, Sack JS, Muckelbauer JK, Chang C, Tredup J, Xie D, Aranibar N, Burke JR, Carter PH, Weinstein DS
Medchemcomm 8 700-712 (2017)
PMID: 30108788

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-151548 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Non-receptor tyrosine-protein kinase TYK2 Chains: A, B
Molecule details ›
Chains: A, B
Length: 298 amino acids
Theoretical weight: 33.31 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P29597 (Residues: 575-869; Coverage: 25%)
Gene name: TYK2
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand 7GL 2 x 7GL
Ligand SO4 3 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P21
Unit cell:
a: 69.599Å b: 65.702Å c: 74.702Å
α: 90° β: 112.42° γ: 90°
R-values:
R R work R free
0.193 0.192 0.215
Expression system: Spodoptera frugiperda

Quick links

Citations

8 review citations

Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase.
Hubbard SR. (2017)
7 more

2 mentions without citation

Prospects for pharmacological targeting of pseudokinases.
Kung et al. (2019)
1 more