› 6oac

X-ray diffraction
3.15Å resolution

PQR530 [(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine] bound to the PI3Ka catalytic subunit p110alpha

Released:
DOI: 10.2210/pdb6oac/pdb
PDB entry 6oac coloured by chain, front view.
PDB entry 6oac coloured by chain, side view.
PDB entry 6oac coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class I PI3K and mTOR Kinase.
Rageot D, Bohnacker T, Keles E, McPhail JA, Hoffmann RM, Melone A, Borsari C, Sriramaratnam R, Sele AM, Beaufils F, Hebeisen P, Fabbro D, Hillmann P, Burke JE, Wymann MP
J Med Chem 62 6241-6261 (2019)
PMID: 31244112

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:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-154615 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Chain: A
Molecule details ›
Chain: A
Length: 948 amino acids
Theoretical weight: 110.2 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P42336 (Residues: 105-1048; Coverage: 88%)
Gene name: PIK3CA
Sequence domains:

Ligands and Environments

1 bound ligand:
Ligand M1J 1 x M1J
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL14-1
Spacegroup: P212121
Unit cell:
a: 58.926Å b: 135.511Å c: 144.498Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.245 0.242 0.287
Expression system: Spodoptera frugiperda

Quick links

Citations

4 review citations

PI3K inhibitors are finally coming of age.
Vanhaesebroeck et al. (2021)
3 more

19 mentions without citation

Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines.
Berti et al. (2018)
18 more