Solution structure of a conformationally constrained Arg-Gly-Asp-like motif inserted into the α/β scaffold of leiurotoxin I

Esther Kellenberger, Georges Mer, Christine Kellenberger, Gérard Marguerie, Jean François Lefèvre

Research output: Contribution to journalArticle

7 Scopus citations


A monoclonal antibody, AC7, directed against the RGD-binding site of the GPIIIa subunit of the platelet fibrinogen receptor, interacts with activated platelet. The H3 region (H3, RQMIRGYFDV sequence) of the complementarity- determining region 3 heavy chain of AC7 inhibits platelet aggregation and fibrinogen binding to platelet. H3 contains the arginine, glycine and aspartate residues, but in an unusual order. The solution structure of the decapeptide has been studied by proton NMR. The NMR data suggested a helical equilibrium. To test whether the helical structure of H3 was biologically relevant, a conformationally constrained peptide with the RGD-like motif was designed. The sequence of a scorpion toxin (leiurotoxin I) has been modified in order to constrain the H3 sequence in a rigid helical conformation. The structure of leiurotoxin I consists of a β-sheet and an α-helix, linked by three disulfide bridges. The structural feature of the chimeric peptide (H3- leiurotoxin) has been determined by standard two-dimensional NMR techniques. H3-Leiurotoxin structure closely resembles that of leiurotoxin I.

Original languageEnglish (US)
Pages (from-to)810-817
Number of pages8
JournalEuropean Journal of Biochemistry
Issue number3
StatePublished - Mar 15 1999



  • Anti-(GpIIb- IIIa) antibody
  • Leiurotoxin I
  • NMR solution structure
  • Protein engineering

ASJC Scopus subject areas

  • Biochemistry

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