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J Proteome Res. 2018 Aug 3;17(8):2695-2703. doi: 10.1021/acs.jproteome.8b00132. Epub 2018 Jul 11.

Cone Snail Glutaminyl Cyclase Sequences from Transcriptomic Analysis and Mass Spectrometric Characterization of Two Pyroglutamyl Conotoxins.

Author information

1
Molecular Biophysics Unit , Indian Institute of Science , Bangalore 560012 , India.
2
National Centre for Biological Sciences , Tata Institute of Fundamental Research , Bangalore 560065 , India.
3
Department of Molecular Biology , Kannur University , Nileshwaram Campus , Kasargod 671314 , Kerala , India.

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.

KEYWORDS:

cone snails; conotoxins; glutaminyl cyclase; mass spectrometry; post-translational modifications; pyroglutamic acid; transcriptome analysis

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