Journal article

Role of disulfide bridges in the folding, structure and biological activity of omega-conotoxin GVIA

JP Flinn, PK Pallaghy, MJ Lew, R Murphy, JA Angus, RS Norton

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | ELSEVIER SCIENCE BV | Published : 1999

Abstract

Omega-Conotoxin GVIA (GVIA), an N-type calcium channel blocker from the cone shell Conus geographus, is a 27 residue polypeptide cross-linked by three disulfide bonds. Here, we report the synthesis, structural analysis by (1)H NMR and bioassay of analogues of GVIA with disulfide bridge deletions and N- and C-terminal truncations. Two analogues that retain the crucial Lys-2 and Tyr-13 residues in loops constrained by two native disulfide bridges were synthesised using orthogonal protection of cysteine residues. In the first analogue, the Cys-15-Cys-26 disulfide bridge was deleted (by replacing the appropriate Cys residues with Ser), while in the second, this disulfide bridge and the eight C-t..

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University of Melbourne Researchers