Mechanistic Investigations of Lysine-Tryptophan Cross-Link Formation Catalyzed by Streptococcal Radical S-Adenosylmethionine Enzymes.
Mechanistic Investigations of Lysine-Tryptophan Cross-Link Formation Catalyzed by Streptococcal Radical S-Adenosylmethionine Enzymes.
复制标题
链球菌自由基 S-腺苷甲硫氨酸酶催化赖氨酸-色氨酸交联形成的机理研究。
DOI：
10.1021/acs.biochem.7b01147
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发表时间：
2018
期刊：
影响因子：
2.9
通讯作者：
Seyedsayamdost,MohammadR
中科院分区：
文献类型：
--
作者：
Schramma,KelseyR;Forneris,ClarissaC;Caruso,Alessio;Seyedsayamdost,MohammadR
Streptide is a ribosomally synthesized and post-translationally modified peptide with a unique cyclization motif consisting of an intramolecular lysine–tryptophan cross-link. Three radicalS-adenosylmethionine enzymes, StrB, AgaB, and SuiB from different species ofStreptococcus, have been shown to install this modification onto their respective precursor peptides in a leader-dependent fashion. Herein, we conduct detailed investigations to differentiate among several plausible mechanistic proposals, specifically addressing radical versus electrophilic addition to the indole during cross-link formation, the role of substrate side chains in binding in the enzyme active site, and the identity of the catalytic base in the reaction cycle. Our results are consistent with a radical electrophilic aromatic substitution mechanism for the key carbon–carbon bond-forming step. They also elaborate on other mechanistic features that underpin this unique and synthetically challenging post-translational modification.
