› 3tl5

X-ray diffraction
2.79Å resolution

Discovery of GDC-0980: a Potent, Selective, and Orally Available Class I Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor for the Treatment of Cancer

Released:
DOI: 10.2210/pdb3tl5/pdb
PDB entry 3tl5 coloured by chain, front view.
PDB entry 3tl5 coloured by chain, side view.
PDB entry 3tl5 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer.
Sutherlin DP, Bao L, Berry M, Castanedo G, Chuckowree I, Dotson J, Folks A, Friedman L, Goldsmith R, Gunzner J, Heffron T, Lesnick J, Lewis C, Mathieu S, Murray J, Nonomiya J, Pang J, Pegg N, Prior WW, Rouge L, Salphati L, Sampath D, Tian Q, Tsui V, Wan NC, Wang S, Wei B, Wiesmann C, Wu P, Zhu BY, Olivero A
J Med Chem 54 7579-87 (2011)
PMID: 21981714

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 980 1 x 980
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: C2
Unit cell:
a: 140.865Å b: 67.012Å c: 105.812Å
α: 90° β: 96.77° γ: 90°
R-values:
R R work R free
0.203 0.199 0.267
Expression system: Spodoptera frugiperda

Quick links

Citations

29 review citations

Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors.
LoRusso PM. (2016)
28 more

3 mentions without citation

Curcumin and Its Analogs in Non-Small Cell Lung Cancer Treatment: Challenges and Expectations.
Tang et al. (2022)
2 more