I1-superfamily conotoxins and prediction of single D-amino acid occurrence

The considerable diversity of Conus peptides in the I-1-superfamily provides a rare opportunity to define parameters important for the post-translational L- to D-isomerization of amino acids. This subtlest of post-translational modifications is not readily detectable by most techniques, and it would be a considerable advance if one could predict its potential occurrence purely from gene sequences. We previously described three I-1-conotoxins, i-RXIA (formerly designated r11a), r11b and r11c, each containing a D-amino acid at the third position from the C-terminus. In this work, we investigated two novel I-1-superfamily members, r11d and ar11a, which we show have only L-amino acids. Based on these observations and an analysis of cDNA sequences of other group members, we suggest that there is a rule to predict D-amino acids in I-1-superfamily peptides. Two factors are important: the residue to be modified should be three amino acids from the C-terminus of the precursor sequence, and it should be in a suitable sequence context. We apply the rule to other members of the I-1-superfarnily, to determine a priori which are probably modified. (c) 2007 Elsevier Ltd. All rights reserved.