› 8sbj

X-ray diffraction
3.1Å resolution

Co-structure Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform complexed with brain penetrant inhibitors

Released:
DOI: 10.2210/pdb8sbj/pdb
PDB entry 8sbj coloured by chain, front view.
PDB entry 8sbj coloured by chain, side view.
PDB entry 8sbj coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of Brain-Penetrant ATP-Competitive mTOR Inhibitors for CNS Syndromes.
Bonazzi S, Gray A, Thomsen NM, Biag J, Labbe-Giguere N, Keaney EP, Malik HA, Sun Y, Nunez J, Karki RG, Knapp M, Elling R, Fuller J, Pardee G, Craig L, Capre K, Salas S, Gorde A, Liang G, Lubicka D, McTighe SM, Goold C, Liu S, Deng L, Hong J, Fekete A, Stadelmann P, Frieauff W, Elhajouji A, Bauer D, Lerchner A, Radetich B, Furet P, Piizzi G, Burdette D, Wilson CJ, Peukert S, Hamann LG, Murphy LO, Curtis D
J Med Chem (2023)
PMID: 37399505

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:

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: Baculovirus expression vector pFastBac1-HM
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: Baculovirus expression vector pFastBac1-HM
UniProt:
  • Canonical: P27986 (Residues: 306-593; Coverage: 40%)
  • Best match: P27986-3 (Residues: 1-293)
Gene names: GRB1, PIK3R1
Sequence domains:

Ligands and Environments

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

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P212121
Unit cell:
a: 100.022Å b: 107.75Å c: 133.868Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.209 0.207 0.257
Expression system: Baculovirus expression vector pFastBac1-HM

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