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Publication Abstract from PubMed

Sactipeptides are ribsomally-produced peptides that contain a characteristic thioether bridge (sactionine bond) that is installed posttranslationally and is absolutely required for their antibiotic activity. Sactipeptide biosynthesis requires a unique class of radical SAM enzymes that contain multiple [4Fe-4S] clusters to form the requisite thioether bridge between a cysteine and the alpha-carbon of an opposing amino acid through radical chemistry. Here we present the structure of the sactionine bond forming enzyme CteB, from Clostridium thermocellum ATCC 27405, with both SAM and an N-terminal fragment of it's peptidyl-substrate at 2.3 A resolution. CteB has the characteristic (beta/alpha)6-TIM barrel fold of radical SAM enzymes, as well as a C-terminal SPASM domain that binds two auxiliary [4Fe-4S] clusters. Importantly, one [4Fe-4S] cluster in the SPASM domain contains an open coordination site, which the peptidyl-cysteine residue undergoing thioether bond formation can potentially coordinate. The crystal structure of CteB also has an accessory N-terminal domain that has high structural similarity to a recently discovered motif present in several en-zymes that act on ribosomally-encoded and post-translationally modified peptides (RiPPs), known as a RiPP precursor peptide recognition element (RRE). This crystal structure is the first of a sactionine bond forming enzyme and sheds light on structures and mechanisms of other members of this class such as AlbA or ThnB.

Structural Insights into Thioether Bond Formation in the Biosynthesis of Sactipeptides.,Grove TL, Himes PM, Hwang S, Yumerefendi H, Bonanno JB, Kuhlman B, Almo SC, Bowers AA J Am Chem Soc. 2017 Jul 13. doi: 10.1021/jacs.7b01283. PMID:28704043^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.