3C09: Crystal Structure The Fab Fragment Of Matuzumab (fab72000) In Complex With Domain Iii Of The Extracellular Region Of Egfr

An increasing number of therapeutic antibodies targeting tumors that express the epidermal growth factor receptor (EGFR) are in clinical use or late stages of clinical development. Here we investigate the molecular basis for inhibition of EGFR activation by the therapeutic antibody matuzumab (EMD72000). We describe the X-ray crystal structure of the Fab fragment of matuzumab (Fab72000) in complex with isolated domain III from the extracellular region of EGFR. Fab72000 interacts with an epitope on EGFR that is distinct from the ligand-binding region on domain III and from the cetuximab/Erbitux epitope. Matuzumab blocks ligand-induced receptor activation indirectly by sterically preventing the domain rearrangement and local conformational changes that must occur for high-affinity ligand binding and receptor dimerization.
PDB ID: 3C09Download
MMDB ID: 63848
PDB Deposition Date: 2008/1/18
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 3.2  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 3C09: trimeric; determined by author
Molecular Components in 3C09
Label Count Molecule
Proteins (3 molecules)
Matuzumab FAB Light Chain
Molecule annotation
Matuzumab FAB Heavy Chain
Molecule annotation
Epidermal Growth Factor Receptor(Gene symbol: EGFR)
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB