› 3l17

X-ray diffraction
3Å resolution

Discovery of (thienopyrimidin-2-yl)aminopyrimidines as Potent, Selective, and Orally Available Pan-PI3-Kinase and Dual Pan-PI3-Kinase/mTOR Inhibitors for the Treatment of Cancer

Released:
DOI: 10.2210/pdb3l17/pdb
PDB entry 3l17 coloured by chain, front view.
PDB entry 3l17 coloured by chain, side view.
PDB entry 3l17 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer.
Sutherlin DP, Sampath D, Berry M, Castanedo G, Chang Z, Chuckowree I, Dotson J, Folkes A, Friedman L, Goldsmith R, Heffron T, Lee L, Lesnick J, Lewis C, Mathieu S, Nonomiya J, Olivero A, Pang J, Prior WW, Salphati L, Sideris S, Tian Q, Tsui V, Wan NC, Wang S, Wiesmann C, Wong S, Zhu BY
J Med Chem 53 1086-97 (2010)
PMID: 20050669

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 + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
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-155801 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Chain: A
Molecule details ›
Chain: A
Length: 966 amino acids
Theoretical weight: 110.73 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P48736 (Residues: 144-1102; Coverage: 87%)
Gene name: PIK3CG
Sequence domains:
Structure domains:

Ligands and Environments

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

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: C2
Unit cell:
a: 144.095Å b: 67.727Å c: 107.455Å
α: 90° β: 96.07° γ: 90°
R-values:
R R work R free
0.218 0.216 0.271
Expression system: Spodoptera frugiperda

Quick links

Citations

6 review citations

Targeting phosphoinositide 3-kinase signalling in lung cancer.
Wojtalla et al. (2011)
5 more

2 mentions without citation

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