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Updated: May 16, 2026

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
Structures of cyanobactin maturation enzymes define a family of transamidating proteases
Vinayak Agarwal1, Elizabeth Pierce, John McIntosh
1Institute for Genomic Biology, University of Illinois at Urbana Champaign, Champaign, IL 61820, USA.
Abstract:
Cyanobactins, a class of ribosomally encoded macrocylic natural products, are biosynthesized through the proteolytic processing and subsequent N-C macrocylization of ribosomal peptide precursors. Macrocylization occurs through a two-step process in which the first protease (PatA) removes the amino terminal flanking sequence from the precursor to yield a free N terminus of the precursor peptide, and the second protease (PatG) removes the C-terminal flanking sequence and then catalyzes the transamidation reaction to yield an N-C cyclized product. Here, we present the crystal structures of the protease domains of PatA and PatG from the patellamide cluster and of PagA from the prenylagaramide cluster. A comparative structural and biochemical analysis of the transamidating PatG protease reveals the presence of a unique structural element distinct from canonical subtilisin proteases, which may facilitate the N-C macrocylization of the peptide substrate.
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