2fjf
From Proteopedia
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'''Structure of the G6 Fab, a phage derived VEGF binding Fab''' | '''Structure of the G6 Fab, a phage derived VEGF binding Fab''' | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Wiesmann, C.]] | [[Category: Wiesmann, C.]] | ||
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Revision as of 00:58, 4 May 2008
Structure of the G6 Fab, a phage derived VEGF binding Fab
Overview
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.
About this Structure
2FJF is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure-function studies of two synthetic anti-vascular endothelial growth factor Fabs and comparison with the Avastin Fab., Fuh G, Wu P, Liang WC, Ultsch M, Lee CV, Moffat B, Wiesmann C, J Biol Chem. 2006 Mar 10;281(10):6625-31. Epub 2005 Dec 22. PMID:16373345 Page seeded by OCA on Sun May 4 03:58:12 2008
