Solution structures of alpha-conotoxin G1 determined by two-dimensional NMR spectroscopy.
Two-dimensional NMR data have been used to generate solution structures of alpha-conotoxin G1, a potent peptide antagonist of the acetylcholine receptor. Structural information was obtained in the form of proton-proton internuclear distance constraints, and initial structures were produced with a distance geometry algorithm. Energetically more favorable structures were generated by using the distance geometry structures as input for a constrained energy minimization program. The results of both of these calculations indicate that the overall backbone conformation of the molecule is well-defined by the NMR data whereas the side-chain conformations are generally less well-defined. The main structural features derived from the NMR data were the presence of tight turns centered on residues Pro5 and Arg9. The solution structures are compared with previous proposed models of conotoxin G1, and the NMR data are interpreted in conjunction with chemical modification studies and structural properties of other antagonists of the acetylcholine receptor to gain insight into structure-activity relationships in these peptide toxins.
Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215.
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Pardi
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Galdes
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Florance
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Maniconte
D000595:Amino Acid Sequence; D002151:Calorimetry; D020916:Conotoxins; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008433:Mathematics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms; D011487:Protein Conformation; D012996:Solutions
D020916:Conotoxins; D008978:Mollusk Venoms; D012996:Solutions; C029960:conotoxin GI