Open AccessHigh‐resolution solution structure of gurmarin, a sweet‐taste‐suppressing plant polypeptide
Author(s) -
Fletcher Jamie I.,
Dingley Andrew J.,
Smith Ross,
Connor Mark,
Christie MacDonald J.,
King Glenn F.
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00659.x
Subject(s) - chemistry , dihedral angle , antiparallel (mathematics) , gymnema sylvestre , structural motif , crystallography , stereochemistry , biophysics , hydrogen bond , biochemistry , molecule , biology , medicine , physics , organic chemistry , quantum mechanics , magnetic field , traditional medicine
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.