36004-73-6Relevant academic research and scientific papers
The Catalytic Mechanism of the Class C Radical S-Adenosylmethionine Methyltransferase NosN
Ding, Wei,Li, Yongzhen,Zhao, Junfeng,Ji, Xinjian,Mo, Tianlu,Qianzhu, Haocheng,Tu, Tao,Deng, Zixin,Yu, Yi,Chen, Fener,Zhang, Qi
, p. 3857 - 3861 (2017)
S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an SN2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product. Instead, NosN converts SAM into 5′-methylthioadenosine as a direct methyl donor, employing a radical-based mechanism for methylation and releasing 5′-thioadenosine as a co-product. A series of biochemical and computational studies allowed us to propose a comprehensive mechanism for NosN catalysis, which represents a new paradigm for enzyme-catalyzed methylation reactions.
