Radical SAM enzymes are emerging as a major superfamily of biological catalysts involved in the biosynthesis of the broad family of bioactive peptides called ribosomally synthesized and post-translationally-modified peptides (RiPPs). These enzymes have been shown to catalyze unconventional reactions such as methyl transfer to electrophilic carbon atoms, sulfur to Cα-atom thioether bonds or carbon-carbon bond formation. Recently, a novel radical SAM enzyme catalyzing the formation of a lysine-tryptophan bond has been identified in Streptococcus thermophilus and a reaction mechanism has been proposed. By combining site-directed mutagenesis, biochemical assays and spectroscopic analyses, we show here that this enzyme, belonging to the emerging family of SPASM-domain radical SAM enzymes, likely contains three [4Fe-4S] clusters. Notably, our data support that the seven conserved cysteine residues, present within the SPASM-domain, are critical for enzyme activity. In addition, we uncovered the minimum substrate requirements and demonstrate that KW-cyclic peptides are more widespread than anticipated, notably in pathogenic bacteria. Finally, we show a strict specificity of the enzyme for lysine and tryptophan residues and the dependence of an eight-amino acids leader peptide, for activity. Altogether, our study suggests novel mechanistic links among SPASM-domain radical SAM enzymes and supports the involvement of non-cysteinly ligands in the coordination of auxiliary clusters.
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Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
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Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
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Dtsch med Wochenschr DOI: 10.1055/s-0043-100054 Hintergrund und Fragestellung Ein etablierter Weg, die optimale Behandlung von Tumorpatien...
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Deepak Thapa, Vanita Ahuja, Deepanshu Dhiman Indian Journal of Anaesthesia 2017 61(12):1012-1014 from #AlexandrosSfakianakis via Alexa...
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BACKGROUND AND PURPOSE: Dengue is a common arboviral disease, which uncommonly involves the brain. There has been a recent surge in dengu...
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Abstract Limited memory size is considered as a major bottleneck in data centers for intelligent urban computing. It is shown that there e...
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Linked Article: Maintz et al. Br J Dermatol 2017; 176:481–487 . from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader h...
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Publication date: Available online 28 February 2018 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Mo...
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