2FJH

Structure of the B20-4 Fab, a phage derived Fab fragment, in complex with VEGF

2FJH の概要

• エントリーDOI: 10.2210/pdb2fjh/pdb
• 関連するPDBエントリー: 1FLT 2FJF 2FJG
• 分子名称: Vascular endothelial growth factor A, Fab fragment light chain, Fab fragment heavy chain (3 entities in total)
• 機能のキーワード: vegf, fab, protein fab complex, cystine knot, hormone-growth factor-immune system complex, hormone/growth factor/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: Q96NW5
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 118801.16

構造登録者

Wiesmann, C. (登録日: 2006-01-02, 公開日: 2006-02-07, 最終更新日: 2024-11-13)

主引用文献

Fuh, G.,Wu, P.,Liang, W.C.,Ultsch, M.,Lee, C.V.,Moffat, B.,Wiesmann, C.
Structure-function studies of two synthetic anti-vascular endothelial growth factor Fabs and comparison with the Avastin Fab.
J.Biol.Chem., 281:6625-6631, 2006

PubMed Abstract: In the quest to discover new research tools and to develop better agents in the fight against cancer, two antibodies, G6 and B20-4, were isolated from synthetic antibody phage libraries. Unlike the AVASTINtrade mark antibody, a recently approved agent for the treatment of patients with colorectal cancer, B20-4 and G6 bind and block both human and murine vascular endothelial growth factor (VEGF). Here we have analyzed and compared the binding epitopes on VEGF for these three antibodies using alanine-scanning mutagenesis and structural analyses. The epitopes recognized by both synthetic antibodies are conserved between human and mouse VEGF, and they match closely to the receptor epitopes both structurally and functionally. In contrast, the Avastin epitope overlaps minimally with the receptor binding surface and centers around a residue that is not conserved in mouse. Our structural and functional analyses elucidate the cross-species reactivity of all three antibodies and emphasize the potential advantages of antibody generation using phage display as the resulting antibodies do not depend on sequence differences across species and preferentially target natural protein-protein interaction surfaces.

PubMed: 16373345
DOI: 10.1074/jbc.M507783200

実験手法

X-RAY DIFFRACTION (3.1 Å)