› 6b3s

X-ray diffraction
2.8Å resolution

Crystal structure of the Fab fragment of necitumumab (Fab11F8) in complex with domain III from a cetuximab resistant variant of EGFR (sEGFRd3-S468R)

Released:
DOI: 10.2210/pdb6b3s/pdb
PDB entry 6b3s coloured by chain, front view.
PDB entry 6b3s coloured by chain, side view.
PDB entry 6b3s coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab Resistance.
Bagchi A, Haidar JN, Eastman SW, Vieth M, Topper M, Iacolina MD, Walker JM, Forest A, Shen Y, Novosiadly RD, Ferguson KM
Mol Cancer Ther 17 521-531 (2018)
PMID: 29158469

Function and Biology Details

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

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-230714 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (6 distinct):
Epidermal growth factor receptor Chains: A, B, E, I
Molecule details ›
Chains: A, B, E, I
Length: 214 amino acids
Theoretical weight: 23.86 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P00533 (Residues: 335-538; Coverage: 17%)
Gene names: EGFR, ERBB, ERBB1, HER1
Sequence domains: Receptor L domain
Structure domains: Receptor L-domain
Necitumumab Fab Heavy chain Chains: C, F, H, J
Molecule details ›
Chains: C, F, H, J
Length: 222 amino acids
Theoretical weight: 23.55 KDa
Source organism: Homo sapiens
Expression system: Mus musculus
Structure domains: Immunoglobulins
Necitumumab Fab Light chain Chains: D, G, K, L
Molecule details ›
Chains: D, G, K, L
Length: 213 amino acids
Theoretical weight: 23.05 KDa
Source organism: Homo sapiens
Expression system: Mus musculus
Structure domains: Immunoglobulins

Ligands and Environments

Carbohydrate polymer : NEW Components: NAG
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA
Carbohydrate polymer
Carbohydrate polymer : NEW Components: NAG, BMA, MAN
Carbohydrate polymer
1 bound ligand:
Ligand NAG 7 x NAG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 23-ID-D
Spacegroup: P2
Unit cell:
a: 151.943Å b: 80.756Å c: 172.901Å
α: 90° β: 91.5° γ: 90°
R-values:
R R work R free
0.209 0.208 0.245
Expression systems:
  • Spodoptera frugiperda
  • Mus musculus

Quick links

Citations

16 review citations

Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies.
Zhou et al. (2021)
15 more

5 mentions without citation

Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab Resistance.
Bagchi et al. (2018)
4 more