› 5ul1

X-ray diffraction
3Å resolution

The co-structure of 3-amino-6-(4-((1-(dimethylamino)propan-2-yl)sulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide and a rationally designed PI3K-alpha mutant that mimics ATR

Released:
DOI: 10.2210/pdb5ul1/pdb
PDB entry 5ul1 coloured by chain, front view.
PDB entry 5ul1 coloured by chain, side view.
PDB entry 5ul1 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Rationally Designed PI3Kα Mutants to Mimic ATR and Their Use to Understand Binding Specificity of ATR Inhibitors.
Lu Y, Knapp M, Crawford K, Warne R, Elling R, Yan K, Doyle M, Pardee G, Zhang L, Ma S, Mamo M, Ornelas E, Pan Y, Bussiere D, Jansen J, Zaror I, Lai A, Barsanti P, Sim J
J Mol Biol 429 1684-1704 (2017)
PMID: 28433539

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: 125.24 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: P42336 (Residues: 1-1068; Coverage: 100%)
Gene name: PIK3CA
Sequence 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: unidentified baculovirus
UniProt:
  • Canonical: P27986 (Residues: 306-593; Coverage: 40%)
Gene names: GRB1, PIK3R1
Sequence domains:

Ligands and Environments

1 bound ligand:
Ligand 8DY 1 x 8DY
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P212121
Unit cell:
a: 100.431Å b: 108.814Å c: 136.576Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.193 0.19 0.26
Expression system: unidentified baculovirus

Quick links

Citations

1 review citation

Structural Determinants of Isoform Selectivity in PI3K Inhibitors.
Miller et al. (2019)
2 other articles

2 mentions without citation

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