› 4waf

X-ray diffraction
2.39Å resolution

Crystal Structure of a novel tetrahydropyrazolo[1,5-a]pyrazine in an engineered PI3K alpha

Released:
DOI: 10.2210/pdb4waf/pdb
PDB entry 4waf coloured by chain, front view.
PDB entry 4waf coloured by chain, side view.
PDB entry 4waf coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5-a]pyrazines as ATR Inhibitors.
Barsanti PA, Aversa RJ, Jin X, Pan Y, Lu Y, Elling R, Jain R, Knapp M, Lan J, Lin X, Rudewicz P, Sim J, Taricani L, Thomas G, Xiao L, Yue Q
ACS Med Chem Lett 6 37-41 (2015)
PMID: 25589927

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: 1073 amino acids
Theoretical weight: 125.13 KDa
Source organism: Homo sapiens
Expression system: Trichoplusia ni
UniProt:
  • Canonical: P42336 (Residues: 2-1068; 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: Trichoplusia ni
UniProt:
  • Canonical: P27986 (Residues: 306-617; Coverage: 43%)
Gene names: GRB1, PIK3R1
Sequence domains:
Structure domains: Helix Hairpins

Ligands and Environments

1 bound ligand:
Ligand 3K6 1 x 3K6
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 104.483Å b: 106.525Å c: 133.507Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.202 0.199 0.247
Expression system: Trichoplusia ni

Quick links

Citations

3 review citations

Progress towards a clinically-successful ATR inhibitor for cancer therapy.
Barnieh et al. (2021)
2 more

12 mentions without citation

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Vollono et al. (2019)
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