› 5a9u

X-ray diffraction
1.6Å resolution

Structure of C1156Y Mutant Human Anaplastic Lymphoma Kinase in Complex with PF-06463922 ((10R)-7-amino-12-fluoro-2,10,16-trimethyl- 15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11) benzoxadiazacyclotetradecine-3-carbonitrile).

Released:
DOI: 10.2210/pdb5a9u/pdb
PDB entry 5a9u coloured by chain, front view.
PDB entry 5a9u coloured by chain, side view.
PDB entry 5a9u coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.
Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng YL, Liu W, Dardaei L, Frias RL, Schultz KR, Logan J, James LP, Smeal T, Timofeevski S, Katayama R, Iafrate AJ, Le L, McTigue M, Getz G, Johnson TW, Engelman JA
N Engl J Med 374 54-61 (2016)
PMID: 26698910

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:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-193961 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
ALK tyrosine kinase receptor Chain: A
Molecule details ›
Chain: A
Length: 327 amino acids
Theoretical weight: 36.97 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q9UM73 (Residues: 1093-1411; Coverage: 20%)
Gene name: ALK
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: CLSI BEAMLINE 08ID-1
Spacegroup: P212121
Unit cell:
a: 51.754Å b: 57.587Å c: 104.887Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.216 0.215 0.258
Expression system: Spodoptera frugiperda

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Citations

140 review citations

Tumour heterogeneity and resistance to cancer therapies.
Dagogo-Jack et al. (2018)
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4 mentions without citation

Chemical strategies to overcome resistance against targeted anticancer therapeutics.
Pisa et al. (2020)
3 more