› 6p8q

X-ray diffraction
1.9Å resolution

EGFR in complex with a dihydrodibenzodiazepinone allosteric inhibitor.

Released:
DOI: 10.2210/pdb6p8q/pdb
PDB entry 6p8q coloured by chain, front view.
PDB entry 6p8q coloured by chain, side view.
PDB entry 6p8q coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors.
De Clercq DJH, Heppner DE, To C, Jang J, Park E, Yun CH, Mushajiang M, Shin BH, Gero TW, Scott DA, Jänne PA, Eck MJ, Gray NS
ACS Med Chem Lett 10 1549-1553 (2019)
PMID: 31749909

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:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-132701 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Epidermal growth factor receptor Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 327 amino acids
Theoretical weight: 37.39 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P00533 (Residues: 696-1022; Coverage: 28%)
Gene names: EGFR, ERBB, ERBB1, HER1
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

5 bound ligands:
Ligand ANP 1 x ANP
Ligand O57 4 x O57
Ligand MG 5 x MG
Ligand AMP 3 x AMP
Ligand EDO 9 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: BRUKER AXS MICROSTAR
Spacegroup: P1
Unit cell:
a: 57.151Å b: 72.874Å c: 79.927Å
α: 100.16° β: 103.16° γ: 95.61°
R-values:
R R work R free
0.169 0.168 0.195
Expression system: Spodoptera frugiperda

Quick links

Citations

6 review citations

Advances in targeting EGFR allosteric site as anti-NSCLC therapy to overcome the drug resistance.
Maity et al. (2020)
5 more

1 mention without citation

Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives.
Das et al. (2022)