Ji. Fletcher et al., High-resolution solution structure of gurmarin, a sweet-taste-suppressing plant polypeptide, EUR J BIOCH, 264(2), 1999, pp. 525-533
Gurmarin is a 35-residue polypeptide from the Asclepiad vine Gymnema sylves
tre. It has been utilised as a pharmacological tool in the study of sweet-t
aste transduction because of its ability to selectively inhibit the neural
response to sweet tastants in rats. We have chemically synthesised and fold
ed 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 Angstrom and 0.73 +/- 0.09
Angstrom, respectively. Gurmarin adopts a compact structure containing an a
ntiparallel beta-hairpin (residues 22-34), several well-defined beta-turns,
and a cystine-knot motif commonly observed in toxic and inhibitory polypep
tides. Despite striking structural homology with delta-atracotoxin, a spide
r neurotoxin known to slow the inactivation of voltage-gated Na+ channels,
we show that gurmarin has no effect on a variety of voltage-sensitive chann
els.