Open AccessStructure and mechanism for iterative amide N -methylation in the biosynthesis of channel-forming peptide cytotoxins
Author(s) -
D.P. Cogan,
Agneya Bhushan,
Reyvin M. Reyes,
Lingyang Zhu,
Jörn Piel,
Satish K. Nair
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2116578119
Subject(s) - peptide , chemistry , methylation , amide , substrate (aquarium) , selectivity , biochemistry , biophysics , molecule , ion channel , membrane , combinatorial chemistry , stereochemistry , biology , gene , organic chemistry , ecology , receptor , catalysis
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.