The Dual α-Amidation System in Scorpion Venom Glands

Many peptides in scorpion venoms are amidated at their C-termini. This post-translational modification is paramount for the correct biological function of ion channel toxins and antimicrobial peptides, among others. The discovery of canonical amidation sequences in transcriptome-derived scorpion pro...

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Bibliographic Details
Main Authors: Gustavo Delgado-Prudencio, Lourival D. Possani, Baltazar Becerril, Ernesto Ortiz
Format: Article
Language:English
Published: MDPI AG 2019-07-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/11/7/425
Description
Summary:Many peptides in scorpion venoms are amidated at their C-termini. This post-translational modification is paramount for the correct biological function of ion channel toxins and antimicrobial peptides, among others. The discovery of canonical amidation sequences in transcriptome-derived scorpion proproteins suggests that a conserved enzymatic &#945;-amidation system must be responsible for this modification of scorpion peptides. A transcriptomic approach was employed to identify sequences putatively encoding enzymes of the &#945;-amidation pathway. A dual enzymatic &#945;-amidation system was found, consisting of the membrane-anchored, bifunctional, peptidylglycine &#945;-amidating monooxygenase (PAM) and its paralogs, soluble monofunctional peptidylglycine &#945;-hydroxylating monooxygenase (PHM<i>m</i>) and peptidyl-&#945;-hydroxyglycine &#945;-amidating lyase (PAL<i>m</i>). Independent genes encode these three enzymes. Amino acid residues responsible for ion coordination and enzymatic activity are conserved in these sequences, suggesting that the enzymes are functional. Potential endoproteolytic recognition sites for proprotein convertases in the PAM sequence indicate that PAM-derived soluble isoforms may also be expressed. Sequences potentially encoding proprotein convertases (PC1 and PC2), carboxypeptidase E (CPE), and other enzymes of the &#945;-amidation pathway, were also found, confirming the presence of this pathway in scorpions.
ISSN:2072-6651