› 5ubt

X-ray diffraction
2.83Å resolution

CRYSTAL STRUCTURE OF PI3K DELTA IN COMPLEX WITH A 7-(3-(PIPERAZIN-1-YL)PHENYL)PYRROLO[2,1-F][1,2,4] TRIAZIN-4-AMINE DERIVIATINE

Released:
DOI: 10.2210/pdb5ubt/pdb
PDB entry 5ubt coloured by chain, front view.
PDB entry 5ubt coloured by chain, side view.
PDB entry 5ubt coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent and selective PI3Kδ inhibitors.
Qin LY, Ruan Z, Cherney RJ, Dhar TGM, Neels J, Weigelt CA, Sack JS, Srivastava AS, Cornelius LAM, Tino JA, Stefanski K, Gu X, Xie J, Susulic V, Yang X, Yarde-Chinn M, Skala S, Bosnius R, Goldstein C, Davies P, Ruepp S, Salter-Cid L, Bhide RS, Poss MA
Bioorg Med Chem Lett 27 855-861 (2017)
PMID: 28108251

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
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-126247 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Chain: A
Molecule details ›
Chain: A
Length: 1013 amino acids
Theoretical weight: 115.96 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: O00329 (Residues: 17-1029; Coverage: 97%)
Gene name: PIK3CD
Sequence domains:
Phosphatidylinositol 3-kinase regulatory subunit alpha Chain: B
Molecule details ›
Chain: B
Length: 168 amino acids
Theoretical weight: 20.72 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: P27986 (Residues: 432-599; Coverage: 23%)
Gene names: GRB1, PIK3R1
Sequence domains: Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain

Ligands and Environments

1 bound ligand:
Ligand 85S 1 x 85S
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P212121
Unit cell:
a: 90.662Å b: 108.603Å c: 142.903Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.216 0.215 0.268
Expression system: unidentified baculovirus

Quick links

Citations

2 review citations

Pyrrolo[2,1-f][1,2,4]triazine: a promising fused heterocycle to target kinases in cancer therapy.
Singh et al. (2022)
1 more

4 mentions without citation

Structural Determinants of Isoform Selectivity in PI3K Inhibitors.
Miller et al. (2019)
3 more