Structural characterization of five post-translationally modified isomorphs of a novel putative δ-conotoxin from the vermivorous snail Conus delessertii from the Mexican Caribbean Sea

A novel peptide, de7b, was isolated from the venom of Conus delessertii, a worm-hunting species collected in the Caribbean Sea off the Yucatan Peninsula. Its primary structure was determined by automated Edman degradation and confirmed by mass spectrometry: it contains 28 amino acids, including six Cys residues. Peptide de7b is the second, O-conotoxin-like peptide isolated from the venom of this species, and it exists in different post-translationally modified isomorphs, some of which contain gamma-carboxy-glutamate (γ) and/or 4-hydroxy-proline (O) at positions 4, 7, and/or 14. Its primary structure is DCI(P/O)GG(E/γ)NCDVFR(O/P)YRCCSGYCILLLCA, with molecular masses varying from 3078.6 to 3154.6 Da, depending on the number and kind of modified amino acid residues. Peptide de7b shows significant sequence identity with several O-conotoxins purified and biologically characterized from molluscivorous and piscivorous cone snails of the Indo-Pacific region, the tropical Atlantic and Eastern Pacific Oceans, especially with the δ-conotoxins but also with the ω-conotoxins from molluscivorous species, which suggests that it might affect voltage-gated Na+ or Ca2+channels. Peptide de7b has 32% sequence identity with putative γ-conotoxin de7a, previously characterized from the same species; both peptides contain the same number of amino acid residues and of non-Cys residues between the pairs of consecutive Cys residues. However, these peptides have charge differences at seven positions within the N-terminal half indicating that they might have distinct molecular targets that remain to be identified.