Crystal structures of novel vascular endothelial growth factors (VEGF) from snake venoms: insight into selective VEGF binding to kinase insert domain-containing receptor but not to fms-like tyrosine kinase-1

J Biol Chem. 2005 Jan 21;280(3):2126-31. doi: 10.1074/jbc.M411395200. Epub 2004 Nov 12.


Vascular endothelial growth factor-A (VEGF-A(165)) exerts multiple effects upon binding to the fms-like tyrosine kinase-1 (Flt-1) and the kinase insert domain-containing receptor (KDR). We recently identified two novel snake venom VEGFs (vammin and VR-1) having unique properties. These VEGFs, designated VEGF-Fs, are highly specific ligands for the kinase insert domain-containing receptor and exhibit potent biological activity both in vitro and in vivo when compared with VEGF-A(165). Here, we solved the crystal structures of vammin and VR-1 at 1.9 and 2.0 A resolutions, respectively. Both structures are very similar to each other, and these structures exhibit similar but significantly different features from the known structures of other VEGFs. These differences include a conformational difference in receptor-binding loop 3 caused by an amino acid residue insertion and a difference in surface potential on the possible binding surface for domain 3 of the receptor. These structural differences may be related to the highly selective ligand properties of VEGF-F.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism*
  • Sequence Homology, Amino Acid
  • Snake Venoms / chemistry*
  • Vascular Endothelial Growth Factor A / chemistry*
  • Vascular Endothelial Growth Factor A / metabolism


  • Snake Venoms
  • Vascular Endothelial Growth Factor A
  • Receptor, Macrophage Colony-Stimulating Factor

Associated data

  • PDB/1WQ8
  • PDB/1WQ9