The molecular mechanism of aminopropylation of peptide-nucleotide antibiotic microcin C

Alexey Kulikovsky, Marina Serebryakova, Olga Bantysh, Anastasia Metlitskaya, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley

    Research output: Contribution to journalArticlepeer-review

    18 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)11168-11175
    Number of pages8
    JournalJournal of the American Chemical Society
    Issue number31
    Publication statusPublished - 6 Aug 2014


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