title: High-resolution solution structure of gurmarin, a sweet-taste-suppressing plant polypeptide.
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 A and 0.73 +/- 0.09 A, respectively. Gurmarin adopts a compact structure containing an antiparallel beta-hairpin (residues 22-34), several well-defined beta-turns, and a cystine-knot motif commonly observed in toxic and inhibitory polypeptides. Despite striking structural homology with delta-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.
authors.affiliation: Department of Biochemistry, University of Sydney, Australia.
authors.forename: J I
authors.initials: JI
authors.lastname: Fletcher
authors.forename: A J
authors.initials: AJ
authors.lastname: Dingley
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Connor
authors.forename: M J
authors.initials: MJ
authors.lastname: Christie
authors.forename: G F
authors.initials: GF
authors.lastname: King
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology; D010940:Plant Proteins / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013649:Taste / Q000187:drug effects
chemical_list: D004220:Disulfides; D007473:Ion Channels; D009498:Neurotoxins; D010940:Plant Proteins; C075206:Gurmarin protein, Gymnema sylvestre