› 4z16

X-ray diffraction
2.9Å resolution

Crystal Structure of the Jak3 Kinase Domain Covalently Bound to N-(3-(((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)methyl)phenyl)acrylamide

Released:
DOI: 10.2210/pdb4z16/pdb
PDB entry 4z16 coloured by chain, front view.
PDB entry 4z16 coloured by chain, side view.
PDB entry 4z16 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Development of Selective Covalent Janus Kinase 3 Inhibitors.
Tan L, Akahane K, McNally R, Reyskens KM, Ficarro SB, Liu S, Herter-Sprie GS, Koyama S, Pattison MJ, Labella K, Johannessen L, Akbay EA, Wong KK, Frank DA, Marto JA, Look TA, Arthur JS, Eck MJ, Gray NS
J Med Chem 58 6589-606 (2015)
PMID: 26258521

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-156548 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Tyrosine-protein kinase JAK3 Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 316 amino acids
Theoretical weight: 35.96 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P52333 (Residues: 811-1124; Coverage: 28%)
Gene name: JAK3
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 4LH 4 x 4LH
1 modified residue:
Ligand PTR 8 x PTR

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 24-ID-E
Spacegroup: P1
Unit cell:
a: 57.625Å b: 68.207Å c: 93.13Å
α: 92.64° β: 93.06° γ: 86.2°
R-values:
R R work R free
0.204 0.202 0.24
Expression system: Trichoplusia ni

Quick links

Citations

11 review citations

The Cysteinome of Protein Kinases as a Target in Drug Development.
Chaikuad et al. (2018)
10 more

9 mentions without citation

Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket.
Forster et al. (2016)
8 more