› 4uxl

X-ray diffraction
2.4Å resolution

Structure of Human ROS1 Kinase Domain in Complex with PF-06463922

Released:
DOI: 10.2210/pdb4uxl/pdb
PDB entry 4uxl coloured by chain, front view.
PDB entry 4uxl coloured by chain, side view.
PDB entry 4uxl coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.
Zou HY, Li Q, Engstrom LD, West M, Appleman V, Wong KA, McTigue M, Deng YL, Liu W, Brooun A, Timofeevski S, McDonnell SR, Jiang P, Falk MD, Lappin PB, Affolter T, Nichols T, Hu W, Lam J, Johnson TW, Smeal T, Charest A, Fantin VR
Proc Natl Acad Sci U S A 112 3493-8 (2015)
PMID: 25733882

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-140438 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Proto-oncogene tyrosine-protein kinase ROS Chain: A
Molecule details ›
Chain: A
Length: 322 amino acids
Theoretical weight: 37.01 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P08922 (Residues: 1934-2232; Coverage: 13%)
Gene names: MCF3, ROS, ROS1
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 5P8 1 x 5P8
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P64
Unit cell:
a: 105.844Å b: 105.844Å c: 49.843Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.211 0.211 0.281
Expression system: Spodoptera frugiperda

Quick links

Citations

59 review citations

Lung cancer: current therapies and new targeted treatments.
Hirsch et al. (2017)
58 more

9 mentions without citation

An overview of kinase downregulators and recent advances in discovery approaches.
Wang et al. (2021)
8 more