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2vwe
From Proteopedia
| 2vwe, resolution 3.40Å () | |||||||||
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| Related: | 2c7w | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
CRYSTAL STRUCTURE OF VASCULAR ENDOTHELIAL GROWTH FACTOR-B IN COMPLEX WITH A NEUTRALIZING ANTIBODY FAB FRAGMENT
Vascular endothelial growth factor (VEGF) B effects blood vessel formation by binding to VEGF receptor 1. To study the specifics of the biological profile of VEGF-B in both physiological and pathological angiogeneses, a neutralising anti-VEGF-B antibody (2H10) that functions by inhibiting the binding of VEGF-B to VEGF receptor 1 was developed. Here, we present the structural features of the 'highly ordered' interaction of the Fab fragment of this antibody (Fab-2H10) with VEGF-B. Two molecules of Fab-2H10 bind to symmetrical binding sites located at each pole of the VEGF-B homodimer, giving a unique U-shaped topology to the complex that has not been previously observed in the VEGF family. VEGF-B residues essential for binding to the antibody are contributed by both monomers of the cytokine. Our detailed analysis reveals that the neutralising effect of the antibody occurs by virtue of the steric hindrance of the receptor-binding interface. These findings suggest that functional complementarity between VEGF-B and 2H10 can be harnessed both in analysing the therapeutic potential of VEGF-B and as an antagonist of receptor activation.
Crystal Structure of Vascular Endothelial Growth Factor-B in Complex with a Neutralising Antibody Fab Fragment., Leonard P, Scotney PD, Jabeen T, Iyer S, Fabri LJ, Nash AD, Acharya KR, J Mol Biol. 2008 Oct 9. PMID:18930733
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2VWE is a 6 chains structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
See VEGF for additional structural information.
Reference
- Leonard P, Scotney PD, Jabeen T, Iyer S, Fabri LJ, Nash AD, Acharya KR. Crystal structure of vascular endothelial growth factor-B in complex with a neutralising antibody Fab fragment. J Mol Biol. 2008 Dec 31;384(5):1203-17. Epub 2008 Oct 9. PMID:18930733 doi:10.1016/j.jmb.2008.09.076
Page seeded by OCA on Tue Feb 17 22:08:35 2009
Categories: Homo sapiens | Mus musculus | Acharya, K R. | Fabri, L J. | Iyer, S. | Jabeen, T. | Leonard, P. | Nash, A D. | Scotney, P D. | Alternative splicing | Angiogenesis | Cysteine-knot | Glycoprotein | Growth factor | Heparin-binding | Immune system | Mitogen | Neutralizing antibody | Secreted | Vegf-b
