› 4rg0

X-ray diffraction
2.5Å resolution

Crystal structure of BTK kinase domain complexed with 2-[8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-(4-methylpiperazin-1-yl)-2-pyridyl]amino]-6-oxo-3-pyridyl]phenyl]-1-oxo-3,4-dihydroisoquinolin-6-yl]-2-methyl-propanenitrile

Released:
DOI: 10.2210/pdb4rg0/pdb
PDB entry 4rg0 coloured by chain, front view.
PDB entry 4rg0 coloured by chain, side view.
PDB entry 4rg0 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Finding the perfect spot for fluorine: improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold.
Lou Y, Sweeney ZK, Kuglstatter A, Davis D, Goldstein DM, Han X, Hong J, Kocer B, Kondru RK, Litman R, McIntosh J, Sarma K, Suh J, Taygerly J, Owens TD
Bioorg Med Chem Lett 25 367-71 (2015)
PMID: 25466710

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-170299 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Tyrosine-protein kinase BTK Chain: A
Molecule details ›
Chain: A
Length: 283 amino acids
Theoretical weight: 32.52 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q06187 (Residues: 378-659; Coverage: 43%)
Gene names: AGMX1, ATK, BPK, BTK
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 3P0 1 x 3P0
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL9-2
Spacegroup: P21212
Unit cell:
a: 71.937Å b: 106.339Å c: 38.429Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.203 0.199 0.282
Expression system: Spodoptera frugiperda

Quick links

Citations

2 review citations

Investigational Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis.
Norman P. (2016)
1 more