› 4jps

X-ray diffraction
2.2Å resolution

Co-crystal Structures of the Lipid Kinase PI3K alpha with Pan and Isoform Selective Inhibitors

Released:
DOI: 10.2210/pdb4jps/pdb
PDB entry 4jps coloured by chain, front view.
PDB entry 4jps coloured by chain, side view.
PDB entry 4jps coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation.
Furet P, Guagnano V, Fairhurst RA, Imbach-Weese P, Bruce I, Knapp M, Fritsch C, Blasco F, Blanz J, Aichholz R, Hamon J, Fabbro D, Caravatti G
Bioorg Med Chem Lett 23 3741-8 (2013)
PMID: 23726034

Function and Biology Details

Reactions catalysed: 
ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-151133 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Chain: A
Molecule details ›
Chain: A
Length: 1074 amino acids
Theoretical weight: 125.29 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P42336 (Residues: 1-1068; Coverage: 100%)
Gene name: PIK3CA
Sequence domains:
Structure domains:
Phosphatidylinositol 3-kinase regulatory subunit alpha Chain: B
Molecule details ›
Chain: B
Length: 293 amino acids
Theoretical weight: 35.14 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P27986 (Residues: 307-593; Coverage: 40%)
Gene names: GRB1, PIK3R1
Sequence domains:
Structure domains: Helix Hairpins

Ligands and Environments

2 bound ligands:
Ligand SCN 1 x SCN
Ligand 1LT 1 x 1LT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P212121
Unit cell:
a: 104.865Å b: 106.195Å c: 133.667Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.206 0.205 0.228
Expression system: Spodoptera frugiperda

Quick links

Citations

37 review citations

Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway.
Polivka et al. (2014)
36 more

61 mentions without citation

PI3K inhibitors: review and new strategies.
Zhang et al. (2020)
60 more