I‐conotoxin superfamily revisited

Abstract

The I-conotoxin superfamily (I-Ctx) is known to have four disulfide bonds with the cysteine arrangement C-C-CC-CC-C-C, and the members inhibit or modify ion channels of nerve cells. Recently, Olivera and co-workers (FEBS J. 2005; 272: 4178-4188) have suggested that the previously described I-Ctx should now be divided into two different gene superfamilies, namely, I1 and I2, in view of their having two different types of signal peptides and exhibiting distinct functions. We have revisited the 28 entries presently grouped as I-Ctx in UniProt Swiss-Prot knowledgebase, and on the basis of in silico analysis have divided them into I1 and I2 superfamilies. The sequence analysis has provided a framework for in silico annotation enabling us to carry out computer-based functional characterization of the UniProtKB/TrEMBL entry Q59AA4 from Conus miles and to predict it as a member of the I2 superfamily. Furthermore, we have predicted the mature toxin of this entry and have proposed that it may be an inhibitor of voltage-gated potassium channels.

PredCSF: An Integrated Feature-Based Approach for Predicting Conotoxin Superfamily

“…The I-conotoxin superfamily was not included because there are still some debates about the classification scheme of the I superfamily. For example, some researchers shown that the conotoxins that were previously assigned to the I superfamily should be separated into two different gene superfamilies, namely I1 and I2 [7,18]. The remaining data set included 403 conotoxin sequences from A, M, O, and T superfamilies.…”

“…Because there are distinct characteristics such as highly conserved N-terminal precursor sequence, disulfidecrosslinked and similar mode of actions, conotoxins have been grouped into several different superfamilies, namely, A, I, M, O, T, P, S, J, D, V and C superfamily [1,7]. Each superfamily can further be classified into several families on the basis of the cysteine arrangement.…”

Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from Conus geographus

“…Therefore, the proposed activity of GXIA is consistent with its observed non-paralytic effect. Whilst another I-superfamily member, ViTx1, has been reported to inhibit K V activity, based on theoretical modelling it is suggestive that ViTx1 acts as a pore blocker [19,53]. The obvious future direction will be to test the proposed biological activity of GXIA, as well as ion channel specificity and analyse whether the structural conservation to K V VS toxins translates into conserved pharmacological action.…”

Conotoxins: natural product drug leads

“…The disulfide-rich group, the conotoxins, is classified into superfamilies based on signal sequence homology and are further classified based on their disulfide framework and target. The I and the O superfamilies have been divided into distinct groups, I1, I2, O1, O2, and O3 [96][97][98] in the figure as a consequence of each having unique signal sequences. Although I1 and I2 have distinct signal sequences, they both have the same frameworks and targets.…”