9lyh

Solution NMR structure of the rosin A1 lanthipeptide

spinqualitylabelsall models 9lyh Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9lyh is a 1 chain structure with sequence from Microbispora. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Ligands: 2KT, DAL, DBB, DBU, TEE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 2-Aminovinyl-cysteine (AviCys) motifs represent a unique class of macrocyclic structures found in many ribosomally synthesized and post-translationally modified peptides (RiPPs). Despite their essential role in bioactivity, their biosynthetic machinery, particularly the cyclases catalyzing Avi-(Me)-Cys macrocyclization, has not been fully characterized. Herein, we report the discovery and biosynthetic elucidation of class V lanthipeptides rosin A1-A3, which feature a lanthionine (Lan) macrocycle and a C-terminal 2-aminovinyl-3-methyl-cysteine (AviMeCys) macrocycle. Rosins promote the migration of human foreskin fibroblast (HSF) cells, representing the first examples of lanthipeptides with cell migration-promoting activity. Comprehensive in vitro reconstitution revealed that the regio- and stereoselective AviMeCys macrocyclization is catalyzed by RosX, a newly identified cyclase with a kinase-like fold. Therefore, RosX-like cyclases, originally misannotated as kinase-like proteins, represent a unique class of cyclases that utilize the enethiol group for AviCys/AviMeCys macrocyclization. Furthermore, we demonstrate that Lan formation in rosins follows a substrate-controlled cyclization pathway with kinetic acceleration by the complex of kinase RosK and lyase RosY, which is distinct from the AviMeCys macrocyclization. This study resolves the long-standing ambiguity of enzymatic AviCys macrocyclization and provides a basis for biosynthetic exploration and bioengineering of AviCys-containing natural products across RiPP subfamilies. A Unique Class of Cyclases with a Kinase Fold Catalyzes Enethiol-Mediated Macrocyclization of Aminovinyl-Cysteine Motifs in Lanthipeptides.,Xie XQ, Guo W, Xia YZ, Liao LJ, Sun MX, Wang JX, Gao JT, Yao HW, Wang H ACS Cent Sci. 2025 Jun 18;11(7):1178-1188. doi: 10.1021/acscentsci.5c00569. , eCollection 2025 Jul 23. PMID:40726796 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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