3C09

Crystal structure the Fab fragment of matuzumab (Fab72000) in complex with domain III of the extracellular region of EGFR

3C09 の概要

• エントリーDOI: 10.2210/pdb3c09/pdb
• 関連するPDBエントリー: 3C08
• 分子名称: Matuzumab Fab Light chain, Matuzumab Fab Heavy chain, Epidermal growth factor receptor, ... (6 entities in total)
• 機能のキーワード: cell surface receptor, glycoprotein, antigen, antibody complex, fab fragment, antitumor, drug immune system-transferase complex, immune system-transferase complex, immune system/transferase
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 144883.62

構造登録者

Ferguson, K.M.,Schmiedel, J.,Knoechel, T. (登録日: 2008-01-18, 公開日: 2008-04-15, 最終更新日: 2024-11-13)

主引用文献

Schmiedel, J.,Blaukat, A.,Li, S.,Knochel, T.,Ferguson, K.M.
Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.
Cancer Cell, 13:365-373, 2008

PubMed Abstract: 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.

PubMed: 18394559
DOI: 10.1016/j.ccr.2008.02.019

実験手法

X-RAY DIFFRACTION (3.2 Å)