9z8j

Gelatinamin A: a figure-of-eight lasso peptide

spinqualitylabelsall models 9z8j Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9z8j is a 1 chain structure with sequence from Brevibacillus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Lasso peptides are structurally unique natural products endowed with high thermal and proteolytic stability, making them attractive as scaffolds for drug discovery. Recently, a new class of lasso peptides containing a second macrocycle, formed between a lysine sidechain and the C-terminus, was discovered, resulting in an even more compact architecture. Here, we report the first NMR structure of the class V lasso peptide, gelatinamin A. Using heterologous expression of the gelatinamin biosynthetic gene cluster (BGC) in Bacillus subtilis, we delineated the biosynthetic pathway through targeted gene deletions. We expressed and characterized the predicted transpeptidase, GelP, that catalyzes the formation of an isopeptide bond between Lys2 and the C-terminus and mediates the reversible conversion of gelatinamin B to gelatinamin A. In addition, we characterize GelT, an N-acetyltransferase that inactivates lasso peptide antimicrobial activity by acetylating a key lysine residue. Furthermore, we demonstrate that gelatinamin is highly potent against several important pathogens and that the activity is strongly bicarbonate-dependent. Finally, we propose a complete biosynthetic pathway for gelatinamin. The structural insight of gelatinamin A and the functional characterization of GelP provide the foundation for future discovery of class V lasso peptides and for engineering transpeptidases to modify other lasso peptide scaffolds. Biosynthesis, Structure, and Antibiotic Properties of Gelatinamin A, a Triculamin-Like Lasso Peptide.,Svenningsen T, Merrild A, Wang F, Hansen FD, Johnson TG, Iwase R, Viennet T, Larsen MK, Link AJ, Torring T Chembiochem. 2026 May 27;27(10):e70378. doi: 10.1002/cbic.70378. PMID:42138325 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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