Matuzumab Binding to EGFR Prevents the Conformational Rearrangement Required for Dimerization

• Published in: Cancer cell Vol. 13; no. 4; pp. 365 - 373
• Main Authors: Schmiedel, Judith, Blaukat, Andree, Li, Shiqing, Knöchel, Thorsten, Ferguson, Kathryn M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2008
• Subjects: Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Binding Sites; Cell Line, Tumor; Cell Membrane - drug effects; Cell Membrane - enzymology; CELLCYCLE; Cetuximab; CHEMBIO; Crystallography, X-Ray; Dimerization; Enzyme Activation - drug effects; Epitopes - chemistry; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - chemistry; ErbB Receptors - metabolism; Humans; Immunoglobulin Fab Fragments - chemistry; Ligands; Models, Molecular; Protein Conformation - drug effects; Protein Structure, Tertiary; PROTEINS; Solubility; PROTEINS; CHEMBIO; CELLCYCLE

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 (EMD720...