title: The molecular mechanism of aminopropylation of peptide-nucleotide antibiotic microcin C.
abstract: Translation inhibitor microcin C (McC) is a heptapeptide with an aspartate α-carboxyl group linked to AMP via phosphoramidate bond. Modification of the McC phosphate by an aminopropyl moiety increases the biological activity by ~10-fold. Here, we determine the pathway of the aminopropylation reaction of McC. We show that the MccD enzyme uses S-adenosyl methionine to transfer 3-amino-3-carboxypropyl group onto a phosphate of an McC maturation intermediate consisting of adenylated heptapeptide. The carboxyl group is removed by the MccE enzyme, yielding mature McC. MccD is an inefficient enzyme that requires for its action the product of Escherichia coli mtn gene, a 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase, which hydrolyses 5'-methylthioadenosine, the product of MccD-catalyzed reaction, thus stimulating the amino-3-carboxypropylation reaction. Both MccD and MccE are capable of modifying McC-like compounds with divergent peptide moieties, opening way for preparation of more potent peptidyl-adenylates.
authors.affiliation: Institute of Gene Biology and ∥Institute of Molecular Genetics, Russian Academy of Sciences , Moscow 119991, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kulikovsky
authors.forename: Marina
authors.initials: M
authors.lastname: Serebryakova
authors.forename: Olga
authors.initials: O
authors.lastname: Bantysh
authors.forename: Anastasia
authors.initials: A
authors.lastname: Metlitskaya
authors.forename: Sergei
authors.initials: S
authors.lastname: Borukhov
authors.forename: Konstantin
authors.initials: K
authors.lastname: Severinov
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dubiley
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D001430:Bacteriocins / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D002264:Carboxylic Acids; C020411:microcin