1. Peptide Macrocyclization Catalyzed by a Prolyl Oligopeptidase Involved in α-Amanitin Biosynthesis.
- Author
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Luo, Hong, Hong, Sung-Yong, Sgambelluri, R. Michael, Angelos, Evan, Li, Xuan, and Walton, Jonathan D.
- Subjects
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PEPTIDES , *RING formation (Chemistry) , *CATALYSIS , *PEPTIDASE , *AMANITINS , *BIOSYNTHESIS , *POST-translational modification - Abstract
Summary Amatoxins are ribosomally encoded and posttranslationally modified peptides that account for the majority of fatal mushroom poisonings of humans. A representative amatoxin is the bicyclic octapeptide α-amanitin, formed via head-to-tail macrocyclization, which is ribosomally biosynthesized as a 35-amino acid propeptide in Amanita bisporigera and in the distantly related mushroom Galerina marginata . Although members of the prolyl oligopeptidase (POP) family of serine proteases have been proposed to play a role in α-amanitin posttranslational processing, the exact mechanistic details are not known. Here, we show that a specific POP (GmPOPB) is required for toxin maturation in G. marginata . Recombinant GmPOPB catalyzed two nonprocessive reactions: hydrolysis at an internal Pro to release the C-terminal 25-mer from the 35-mer propeptide and transpeptidation at the second Pro to produce the cyclic octamer. On the other hand, we show that GmPOPA, the putative housekeeping POP of G. marginata , behaves like a conventional POP. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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