title: 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.
abstract: 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.
authors.affiliation: Department of Biochemistry, National Institute of Agrobiological Sciences, 2-1-2, Kannondai, Tsukuba, Ibaraki 305-8602, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuno
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012910:Snake Venoms / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012910:Snake Venoms; D042461:Vascular Endothelial Growth Factor A; D016186:Receptor, Macrophage Colony-Stimulating Factor