AI Article Synopsis

  • The enzyme glutaminyl cyclase (QC) converts N-terminal glutamine to pyroglutamyl residue in conotoxins from marine cone snails.
  • Four complete and two partial QC sequences were identified from various cone snail species using transcriptomic data, showing high similarity to mammalian enzymes.
  • Mass spectrometry confirmed the presence of pyroglutamyl conotoxins in the venoms of C. frigidus and C. amadis, revealing unique structural frameworks and additional modifications in the peptides.

Article Abstract

The post-translational modification of N-terminal glutamine (Q) to a pyroglutamyl (Z) residue is observed in the conotoxins produced by marine cone snails. This conversion requires the action of the enzyme glutaminyl cyclase (QC). Four complete QC sequences from the species C. araneosus, C. frigidus, C. litteratus, and C. monile and two partial sequences from C. amadis and C. miles have been obtained by analysis of transcriptomic data. Comparisons with mammalian enzyme sequences establish a high level of identity and complete conservation of functional active site residues, including a cluster of hydrogen-bonded acidic side chains. Mass spectrometric analysis of crude venom samples coupled to conotoxin precursor protein sequences obtained from transcriptomic data establishes the presence of pyroglutamyl conotoxins in the venom of C. frigidus and C. amadis. The C. frigidus peptide belongs to the M superfamily, with cysteine framework III, whereas the C. amadis peptide belongs to the divergent superfamily with cysteine framework VI/VII. Additionally, gamma carboxylation of glutamic acid and hydroxylation of proline are observed in the C. frigidus peptide. Mass spectral data are available via ProteomeXchange with identifier PXD009006.

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http://dx.doi.org/10.1021/acs.jproteome.8b00132DOI Listing

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