8cwx

NMR structure of a Stapled Lanthipeptide Natural Product

spinqualitylabelsall models 8cwx Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8cwx is a 1 chain structure with sequence from Streptomyces morookaense. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: DAL, DBB, DBU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A7Y7E8Q0_STRMO Publication Abstract from PubMed Lanthipeptides are a class of cyclic peptides characterized by the presence of one or more lanthionine (Lan) or methyllanthionine (MeLan) thioether rings. These cross-links are produced by alpha,beta-unsaturation of Ser or Thr residues in peptide substrates by dehydration, followed by a Michael-type conjugate addition of Cys residues onto the dehydroamino acids. Lanthipeptides may be broadly classified into at least five different classes, and the biosynthesis of classes I-IV lanthipeptides requires catalysis by LanC cyclases that control both the site-specificity and the stereochemistry of the conjugate addition. In contrast, there are no current examples of LanCs that occur in class V biosynthetic clusters, despite the presence of lanthionine rings in these compounds. In this work, bioinformatics-guided co-occurrence analysis identifies more than 240 putative class V lanthipeptide clusters that contain a LanC cyclase. Reconstitution studies demonstrate that the cyclase-catalyzed product is notably distinct from the product formed spontaneously. Stereochemical analysis shows that the cyclase diverts the final product to a configuration that is distinct from one that is energetically favored. Structural characterization of the final product by multi-dimensional NMR spectroscopy reveals that it forms a helical stapled peptide. Mutational analysis identified a plausible order for cyclization and suggests that enzymatic rerouting to the final structure is largely directed by the construction of the first lanthionine ring. These studies show that lanthipeptide cyclases are needed for the biosynthesis of some constrained peptides, the formations of which would otherwise be energetically unfavored. Class V Lanthipeptide Cyclase Directs the Biosynthesis of a Stapled Peptide Natural Product.,Pei ZF, Zhu L, Sarksian R, van der Donk WA, Nair SK J Am Chem Soc. 2022 Sep 28;144(38):17549-17557. doi: 10.1021/jacs.2c06808. Epub , 2022 Sep 15. PMID:36107785 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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