› 5fi4

X-ray diffraction
2.5Å resolution

Discovery of imidazo[1,2-a]-pyridine inhibitors of pan-PI3 kinases that are efficacious in a mouse xenograft model

Released:
DOI: 10.2210/pdb5fi4/pdb
PDB entry 5fi4 coloured by chain, front view.
PDB entry 5fi4 coloured by chain, side view.
PDB entry 5fi4 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of imidazo[1,2-a]-pyridine inhibitors of pan-PI3 kinases that are efficacious in a mouse xenograft model.
Han W, Menezes DL, Xu Y, Knapp MS, Elling R, Burger MT, Ni ZJ, Smith A, Lan J, Williams TE, Verhagen J, Huh K, Merritt H, Chan J, Kaufman S, Voliva CF, Pecchi S
Bioorg Med Chem Lett 26 742-746 (2016)
PMID: 26774655

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: 323 amino acids
Theoretical weight: 38.74 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P27986 (Residues: 306-617; Coverage: 43%)
Gene names: GRB1, PIK3R1
Sequence domains:
Structure domains: Helix Hairpins

Ligands and Environments

2 bound ligands:
Ligand GOL 1 x GOL
Ligand 5XV 1 x 5XV
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 105.2Å b: 105.32Å c: 134.39Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.196 0.194 0.245
Expression system: Spodoptera frugiperda

Quick links

Citations

4 citation in other articles

Oncogenic mutations of PIK3CA lead to increased membrane recruitment driven by reorientation of the ABD, p85 and C-terminus.
Jenkins et al. (2023)
3 more

4 mentions without citation

Advances in chemical proteomic evaluation of lipid kinases-DAG kinases as a case study.
Ware et al. (2021)
3 more