title: Structures of cyanobactin maturation enzymes define a family of transamidating proteases.
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.
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana Champaign, Champaign, IL 61820, USA.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Agarwal
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pierce
authors.forename: John
authors.initials: J
authors.lastname: McIntosh
authors.forename: Eric W
authors.initials: EW
authors.lastname: Schmidt
authors.forename: Satish K
authors.initials: SK
authors.lastname: Nair
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D010456:Peptides, Cyclic; D011994:Recombinant Proteins; D010447:Peptide Hydrolases