PDBsum entry 2xac

Transferase/signaling protein

PDB id: 2xac

Contents

Protein chains

99 a.a. *

98 a.a. *

Ligands

GOL

Waters ×33

* Residue conservation analysis

PDB id:

2xac

Name:

Transferase/signaling protein

Title:

Structural insights into the binding of vegf-b by vegfr-1d2: recognition and specificity

Structure:

Vascular endothelial growth factor b. Chain: a, b. Fragment: receptor-binding domain, residues 31-129. Synonym: vegf-b, vegf-related factor, vrf. Engineered: yes. Vascular endothelial growth factor receptor 1. Chain: c, x. Fragment: domain 2, residues 129-226. Synonym: vegfr-1, vascular permeability factor receptor, tyrosine-

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 469008.

Resolution:

2.71Å R-factor: 0.286 R-free: 0.364

Authors:

S.Iyer,P.Darley,K.R.Acharya

Key ref:

S.Iyer et al. (2010). Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity. J Biol Chem, 285, 23779-23789. PubMed id: 20501651

Date:

30-Mar-10 Release date: 19-May-10

Protein chains

P49765  (VEGFB_HUMAN) -  Vascular endothelial growth factor B from Homo sapiens

Seq: 207 a.a.

Struc: 99 a.a.

Protein chains

P17948  (VGFR1_HUMAN) -  Vascular endothelial growth factor receptor 1 from Homo sapiens

Seq: 1338 a.a.

Struc: 98 a.a.

Enzyme reactions

• Enzyme class: Chains C, X: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

J Biol Chem 285:23779-23789 (2010)

PubMed id: 20501651

Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity.

S.Iyer, P.I.Darley, K.R.Acharya.

ABSTRACT

The formation of blood vessels (angiogenesis) is a highly orchestrated sequence of events involving crucial receptor-ligand interactions. Angiogenesis is critical for physiological processes such as development, wound healing, reproduction, tissue regeneration and remodeling. It also plays a major role in sustaining tumor progression and chronic inflammation. Vascular Endothelial Growth Factor-B (VEGF-B), a member of the VEGF family of angiogenic growth factors, effects blood vessel formation by binding to a tyrosine kinase receptor, VEGFR-1. There is growing evidence of the important role played by VEGF-B in physiological and pathological vasculogenesis. Development of VEGF-B antagonists, which inhibit the interaction of this molecule with its cognate receptor, would be important for the treatment of pathologies associated specifically with this growth factor. In this study we present the crystal structure of the complex of VEGF-B with domain 2 of VEGFR-1 at 2.7A resolution. Our analysis reveals that each molecule of the ligand engages two receptor molecules using two symmetrical binding sites. Based on these interactions we identify the receptor-binding determinants on VEGF-B and shed light on the differences in specificity towards VEGFR-1 among the different VEGF homologs.