5SX5

Crystal Structure of panitumumab in complex with epidermal growth factor receptor domain 3 mutant S468R.

5SX5 の概要

• エントリーDOI: 10.2210/pdb5sx5/pdb
• 関連するPDBエントリー: 5SX4
• 分子名称: Panitumumab Fab Light Chain, Panitumumab Fab Heavy Chain, Epidermal growth factor receptor, ... (8 entities in total)
• 機能のキーワード: cetuximab, panitumumab, egfr, vectibix, erbitux, transferase-immune system complex, transferase/immune system
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 141231.64

構造登録者

Sickmier, E.A. (登録日: 2016-08-09, 公開日: 2016-10-05, 最終更新日: 2024-11-20)

主引用文献

Sickmier, E.A.,Kurzeja, R.J.,Michelsen, K.,Vazir, M.,Yang, E.,Tasker, A.S.
The Panitumumab EGFR Complex Reveals a Binding Mechanism That Overcomes Cetuximab Induced Resistance.
Plos One, 11:e0163366-e0163366, 2016

PubMed Abstract: Panitumumab and cetuximab target the epidermal growth factor receptor for the treatment of metastatic colorectal cancer. These therapies provide a significant survival benefit to patients with metastatic colorectal cancer with wild-type RAS. A single point mutation in the ectodomain of EGFR (S468R) confers acquired or secondary resistance in cetuximab treated patients, which is not observed in panitumumab-treated patients. Structural and biophysical studies presented here show this mutation directly blocks cetuximab binding to EGFR domain III and describes a unique mechanism by which panitumumab uses a central cavity to accommodate this mutation.

PubMed: 27658254
DOI: 10.1371/journal.pone.0163366

実験手法

X-RAY DIFFRACTION (2.5 Å)