8CAV

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

8CAV の概要

• エントリーDOI: 10.2210/pdb8cav/pdb
• 分子名称: Serine/threonine protein kinase, CuvA, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (6 entities in total)
• 機能のキーワード: lanthipeptide, biosynthetic protein
• 由来する生物種: Thermomonospora curvata; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 198434.05

構造登録者

Sigurdsson, A.,Martins, B.M.,Duettmann, S.A.,Jasyk, M.,Dimos-Roehl, B.,Schoepf, F.,Gemannter, M.,Knittel, C.H.,Schnegotyzki, R.,Schmid, B.,Kosol, S.,Gonzalez-Viegas, M.,Seidel, M.,Huegelland, M.,Leimkuehler, S.,Dobbek, H.,Mainz, A.,Suessmuth, R. (登録日: 2023-01-24, 公開日: 2023-06-14, 最終更新日: 2024-10-23)

主引用文献

Sigurdsson, A.,Martins, B.M.,Duttmann, S.A.,Jasyk, M.,Dimos-Rohl, B.,Schopf, F.,Gemander, M.,Knittel, C.H.,Schnegotzki, R.,Schmid, B.,Kosol, S.,Pommerening, L.,Gonzales-Viegaz, M.,Seidel, M.,Hugelland, M.,Leimkuhler, S.,Dobbek, H.,Mainz, A.,Sussmuth, R.D.
Discovery of the Lanthipeptide Curvocidin and Structural Insights into its Trifunctional Synthetase CuvL.
Angew.Chem.Int.Ed.Engl., 62:e202302490-e202302490, 2023

PubMed Abstract: 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 α-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.

PubMed: 37014271
DOI: 10.1002/anie.202302490

実験手法

X-RAY DIFFRACTION (2.87 Å)