Crystal Structures of Novel Vascular Endothelial Growth Factors (VEGF) from Snake Venoms

Abstract

Vascular endothelial growth factor-A (VEGF-A165) 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 domaincontaining receptor and exhibit potent biological activity both in vitro and in vivo when compared with VEGFA165. Here, we solved the crystal structures of vammin and VR-1 at 1.9 and 2.0 Å 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. [ABSTRACT FROM AUTHOR]