6IPV
Crystal structure of CqsB2 from Streptomyces exfoliatus 2419-SVT2 (apo form)
Summary for 6IPV
| Entry DOI | 10.2210/pdb6ipv/pdb |
| Descriptor | CqsB2 (2 entities in total) |
| Functional Keywords | carquinostatin a biosynthesis, polyketide aromatase/cyclase, biosynthetic protein |
| Biological source | Streptomyces exfoliatus |
| Total number of polymer chains | 4 |
| Total formula weight | 110580.42 |
| Authors | Tomita, T.,Kobayashi, M.,Nishiyama, M.,Kuzuyama, T. (deposition date: 2018-11-05, release date: 2019-10-16, Last modification date: 2024-03-27) |
| Primary citation | Kobayashi, M.,Tomita, T.,Shin-Ya, K.,Nishiyama, M.,Kuzuyama, T. An Unprecedented Cyclization Mechanism in the Biosynthesis of Carbazole Alkaloids in Streptomyces. Angew.Chem.Int.Ed.Engl., 58:13349-13353, 2019 Cited by PubMed Abstract: Carquinostatin A (CQS), a potent neuroprotective substance, is a unique carbazole alkaloid with both an ortho-quinone function and an isoprenoid moiety. We identified the entire gene cluster responsible for CQS biosynthesis in Streptomyces exfoliatus through heterologous production of CQS and gene deletion. Biochemical characterization of seven CQS biosynthetic gene products (CqsB1-7) established the total biosynthetic pathway of CQS. Reconstitution of CqsB1 and CqsB2 showed that the synthesis of the carbazole skeleton involves CqsB1-catalyzed decarboxylative condensation of an α-hydroxyl-β-keto acid intermediate with 3-hydroxybutyryl-ACP followed by CqsB2-catalyzed oxidative cyclization. Based on crystal structures and mutagenesis-based biochemical assays, a detailed mechanism for the unique deprotonation-initiated cyclization catalyzed by CqsB2 is proposed. Finally, analysis of the substrate specificity of the biosynthetic enzymes led to the production of novel carbazoles. PubMed: 31350791DOI: 10.1002/anie.201906864 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
Download full validation report
