High-resolution solution structure of gurmarin, a sweet-taste- suppressing plant polypeptide

Jamie I. Fletcher, Andrew J. Dingley, Ross Smith, Mark Connor, MacDonald J. Christie, Glenn F. King*

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Gurmarin is a 35-residue polypeptide from the Asclepiad vine Gymnema sylvestre. It has been utilised as a pharmacological tool in the study of sweet-taste transduction because of its ability to selectively inhibit the neural response to sweet tastants in rats. We have chemically synthesised and folded gurmarin and determined its three-dimensional solution structure to high resolution using two-dimensional NMR spectroscopy. Structure calculations utilised 612 interproton-distance, 19 dihedral-angle, and 18 hydrogen-bond restraints. The structure is well defined for residues 3-34, with backbone and heavy atom rms differences of 0.27 ± 0.09 Å and 0.73 ± 0.09 Å, respectively. Gurmarin adopts a compact structure containing an antiparallel β-hairpin (residues 22-34), several well-defined β-turns, and a cystine-knot motif commonly observed in toxic and inhibitory polypeptides. Despite striking structural homology with δ-atracotoxin, a spider neurotoxin known to slow the inactivation of voltage-gated Na+ channels, we show that gurmarin has no effect on a variety of voltage-sensitive channels.

Original languageEnglish
Pages (from-to)525-533
Number of pages9
JournalEuropean Journal of Biochemistry
Volume264
Issue number2
DOIs
Publication statusPublished - 1 Sep 1999
Externally publishedYes

Keywords

  • Gurmarin
  • Ion channels
  • NMR
  • Protein structure
  • Sweet-taste suppression

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