3B2U

Crystal structure of isolated domain III of the extracellular region of the epidermal growth factor receptor in complex with the Fab fragment of IMC-11F8

Summary for 3B2U

• Entry DOI: 10.2210/pdb3b2u/pdb
• Related: 3B2V
• Descriptor: IMC-11F8 Fab Light chain, IMC-11F8 Fab Heavy chain, Epidermal growth factor receptor, ... (10 entities in total)
• Functional Keywords: cell surface receptor; glycoprotein; antigen:antibody complex; fab fragment; antitumor; drug, anti-oncogene, atp-binding, cell cycle, disease mutation, kinase, membrane, nucleotide-binding, phosphoprotein, secreted, transferase, transmembrane, tyrosine-protein kinase, immune system-transferase complex, immune system/transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 24
• Total formula weight: 577651.09

Authors

Ferguson, K.M.,Li, S.,Kussie, P. (deposition date: 2007-10-19, release date: 2008-02-19, Last modification date: 2024-10-30)

Primary citation

Li, S.,Kussie, P.,Ferguson, K.M.
Structural basis for EGF receptor inhibition by the therapeutic antibody IMC-11F8.
Structure, 16:216-227, 2008

PubMed Abstract: Therapeutic anticancer strategies that target and inactivate the epidermal growth factor receptor (EGFR) are under intense study in the clinic. Here we describe the mechanism of EGFR inhibition by an antibody drug IMC-11F8. IMC-11F8 is a fully human antibody that has similar antitumor potency as the chimeric cetuximab/Erbitux and might represent a safer therapeutic alternative. We report the X-ray crystal structure of the Fab fragment of IMC-11F8 (Fab11F8) in complex with the entire extracellular region and with isolated domain III of EGFR. We compare this to our previous study of the cetuximab/EGFR interaction. Fab11F8 interacts with a remarkably similar epitope, but through a completely different set of interactions. Both the similarities and differences in binding of these two antibodies have important implications for the development of inhibitors that could exploit this same mechanism of EGFR inhibition.

PubMed: 18275813
DOI: 10.1016/j.str.2007.11.009

Experimental method

X-RAY DIFFRACTION (2.58 Å)