Modelling of the interaction of verotoxin-1 (VT1) with its glycolipid receptor, globotriaosylceramide (Gb3)

Int J Biol Macromol. 1995 Jun;17(3-4):199-204. doi: 10.1016/0141-8130(95)92686-k.

Abstract

Possible binding sites for the glycolipid globotriaosylceramide (Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->1 Cer; Gb3) on the B-subunits of verotoxin-1 (VT1) were explored using binding data for specifically mutated verotoxins and by computational docking of favoured conformers of Gb3 with the crystal structure of VT1. Calculations using the GRID program suggested a site with favourable hydrophobic interactions at the exposed side chain of Phe30. One of the favoured conformers of Gb3 was docked into this site, with the hydrophobic face of the internal Gal beta residue in contact with the side chain of Phe30. After energy minimization, the two terminal saccharide residues of Gb3 (Gal alpha and Gal beta) showed favourable interactions with the toxin. In the proposed model of the complex, the terminal Gal alpha of Gb3 is located in proximity to aspartates 16-18 of VT1. The model is in agreement with available experimental binding data for the interaction of globoglycolipids with different naturally occurring and mutated verotoxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / metabolism*
  • Binding Sites
  • Carbohydrate Conformation*
  • Carbohydrate Sequence
  • Computer Simulation
  • Cytotoxins / chemistry
  • Cytotoxins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Conformation*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Shiga Toxin 1
  • Software
  • Trihexosylceramides / chemistry*
  • Trihexosylceramides / metabolism*

Substances

  • Bacterial Toxins
  • Cytotoxins
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Shiga Toxin 1
  • Trihexosylceramides
  • globotriaosylceramide