› 4otr

X-ray diffraction
1.95Å resolution

Crystal structure of BTK kinase domain complexed with 6-cyclopropyl-2-[3-[5-[[5-(4-ethylpiperazin-1-yl)-2-pyridyl]amino]-1-methyl-6-oxo-3-pyridyl]-2-(hydroxymethyl)phenyl]-8-fluoro-isoquinolin-1-one

Released:
DOI: 10.2210/pdb4otr/pdb
PDB entry 4otr coloured by chain, front view.
PDB entry 4otr coloured by chain, side view.
PDB entry 4otr coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis.
Lou Y, Han X, Kuglstatter A, Kondru RK, Sweeney ZK, Soth M, McIntosh J, Litman R, Suh J, Kocer B, Davis D, Park J, Frauchiger S, Dewdney N, Zecic H, Taygerly JP, Sarma K, Hong J, Hill RJ, Gabriel T, Goldstein DM, Owens TD
J Med Chem 58 512-6 (2015)
PMID: 24712864

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

2 bound ligands:
Ligand 2V3 1 x 2V3
Ligand DMS 2 x DMS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P21212
Unit cell:
a: 71.537Å b: 106.458Å c: 38.265Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.183 0.18 0.229
Expression system: Spodoptera frugiperda

Quick links

Citations

11 review citations

Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy.
Alam et al. (2017)
10 more

2 mentions without citation

A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader.
Huang et al. (2018)
1 more