SkfB Abstracts a Hydrogen Atom from C α on SkfA To Initiate Thioether Cross-Link Formation

作者：Nathan A. Bruender, Vahe Bandarian · 发表于：Biochemistry · 年份：2016 · DOI：10.1021/acs.biochem.6b00598 · 被引用次数：43 · 研究领域：Click Chemistry and Applications、Chemical Synthesis and Analysis、Metalloenzymes and iron-sulfur proteins

Sulfur to α-carbon thioether-containing peptides (sactipeptides) are ribosomally synthesized post-translationally modified peptides with bacteriocidal activities. The thioether cross-link, which is required for biological activity, is installed by a member of the radical S-adenosyl-l-methionine (SAM) superfamily in the peptide substrate. Herein, we show that the radical SAM enzyme, SkfB, utilizes the 5'-deoxyadenosyl radical generated from the reductive cleavage of SAM to abstract a hydrogen atom from the α-carbon of the amino acid at position 12 in the substrate, SkfA, to initiate the installation of a thioether cross-link. The insights from this work can be applied to all radical SAM sactipeptide maturases.