Bruender Nathan A, Bandarian Vahe
Chemistry Department, University of Utah , Salt Lake City, Utah 84112, United States.
Biochemistry. 2016 Aug 2;55(30):4131-4. doi: 10.1021/acs.biochem.6b00598. Epub 2016 Jul 21.
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.
含硫至α-碳硫醚的肽（硫肽）是核糖体合成的具有杀菌活性的翻译后修饰肽。生物活性所需的硫醚交联是由肽底物中自由基S-腺苷-L-甲硫氨酸（SAM）超家族的一个成员安装的。在此，我们表明自由基SAM酶SkfB利用SAM还原裂解产生的5'-脱氧腺苷自由基从底物SkfA中第12位氨基酸的α-碳上提取一个氢原子，以启动硫醚交联的安装。这项工作的见解可应用于所有自由基SAM硫肽成熟酶。
