› 8a27

X-ray diffraction
1.07Å resolution

EGFR kinase domain in complex with 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-[6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl]methyl]phenyl]ethynyl]-1-oxo-4-(trifluoromethyl)isoindolin-2-yl]-N-thiazol-2-yl-acetamide

Released:
DOI: 10.2210/pdb8a27/pdb
PDB entry 8a27 coloured by chain, front view.
PDB entry 8a27 coloured by chain, side view.
PDB entry 8a27 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib.
Obst-Sander U, Ricci A, Kuhn B, Friess T, Koldewey P, Kuglstatter A, Hewings D, Goergler A, Steiner S, Rueher D, Imhoff MP, Raschetti N, Marty HP, Dietzig A, Rynn C, Ehler A, Burger D, Kornacker M, Schaffland JP, Herting F, Pao W, Bischoff JR, Martoglio B, Alice Nagel Y, Jaeschke G
J Med Chem (2022)
PMID: 36178776

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-132671 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Epidermal growth factor receptor Chain: A
Molecule details ›
Chain: A
Length: 326 amino acids
Theoretical weight: 37.23 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P00533 (Residues: 700-1022; Coverage: 27%)
Gene names: EGFR, ERBB, ERBB1, HER1
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

3 bound ligands:
Ligand EDO 3 x EDO
Ligand KY9 1 x KY9
Ligand NO3 2 x NO3
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: C2
Unit cell:
a: 119.28Å b: 34.915Å c: 84.334Å
α: 90° β: 128.92° γ: 90°
R-values:
R R work R free
0.126 0.124 0.16
Expression system: Spodoptera frugiperda

Quick links

Citations

1 review citation

Targeting Epidermal Growth Factor Receptor for Cancer Treatment: Abolishing Both Kinase-Dependent and Kinase-Independent Functions of the Receptor.
Zhang Y. (2023)
2 other articles

4 mentions without citation

Network pharmacology reveals that Berberine may function against Alzheimer's disease via the AKT signaling pathway.
Wei et al. (2023)
3 more