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Structure and mechanism for iterative amide N-methylation in the biosynthesis of channel-forming peptide cytotoxins

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Significance The channel-forming proteusins are bacterial helical peptides that allow permeation of positively charged ions to influence membrane potential and cellular physiology. We biochemically characterize the effect of two critical… Click to show full abstract

Significance The channel-forming proteusins are bacterial helical peptides that allow permeation of positively charged ions to influence membrane potential and cellular physiology. We biochemically characterize the effect of two critical posttranslational modifications on the secondary structure of the peptide substrate. We determine how a methyl group can be added to the side chains of D-Asn residues in a peptide substrate and show how flanking residues influence selectivity. These studies should foster the development of small-molecule peptide ion channels as therapeutics.

Keywords: structure mechanism; iterative amide; mechanism iterative; channel forming; channel

Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022

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