8car

Discovery of the lanthipeptide Curvocidin and structural insights into its trifunctional synthetase CuvL

spinqualitylabelsall models 8car, resolution 2.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8car is a 1 chain structure with sequence from Thermomonospora curvata. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.68Å Ligands: MSE, NO3, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D1A2F7_THECD Publication Abstract from PubMed Lanthipeptides are ribosomally-synthesized natural products from bacteria featuring stable thioether-crosslinks and various bioactivities. Herein, we report on a new clade of tricyclic class-IV lanthipeptides with curvocidin from Thermomonospora curvata as its first representative. We obtained crystal structures of the corresponding lanthipeptide synthetase CuvL that showed a circular arrangement of its kinase, lyase and cyclase domains, forming a central reaction chamber for the iterative substrate processing involving nine catalytic steps. The combination of experimental data and artificial intelligence-based structural models identified the N-terminal subdomain of the kinase domain as the primary site of substrate recruitment. The ribosomal precursor peptide of curvocidin employs an amphipathic alpha-helix in its leader region as an anchor to CuvL, while its substrate core shuttles within the central reaction chamber. Our study thus reveals general principles of domain organization and substrate recruitment of class-IV and class-III lanthipeptide synthetases. Discovery of the Lanthipeptide Curvocidin and Structural Insights into its Trifunctional Synthetase CuvL.,Sigurdsson A, Martins BM, Duttmann SA, Jasyk M, Dimos-Rohl B, Schopf F, Gemander M, Knittel CH, Schnegotzki R, Schmid B, Kosol S, Pommerening L, Gonzales-Viegaz M, Seidel M, Hugelland M, Leimkuhler S, Dobbek H, Mainz A, Sussmuth RD Angew Chem Int Ed Engl. 2023 Jun 5;62(23):e202302490. doi: , 10.1002/anie.202302490. Epub 2023 Apr 27. PMID:37014271 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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