Mechanistic Insights Into Post-Translational α-Keto-β-Amino Acid Formation by a Radical S-Adenosyl Methionine Peptide Splicease.

ABSTRACT: Radical S-adenosyl methionine enzymes catalyze a diverse repertoire of post-translational modifications in protein and peptide substrates. Among these, an exceptional and mechanistically obscure example is the installation of α-keto-β-amino acid residues by formal excision of a tyrosine-derived tyramine unit. The responsible spliceases are key maturases in a widespread family of natural products termed spliceotides that comprise potent protease inhibitors, with the installed β-residues being crucial for bioactivity. Here, we established the in vitro activity of the model splicease PcpXY to interrogate the mechanism of non-canonical protein splicing. Identification of shunt and coproducts, deuterium labeling studies, and density functional theory energy calculations of hypothesized intermed

SUBMITTER: Vagstad AL 

PROVIDER: S-EPMC11879070 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature