6ipw

Crystal structure of CqsB2 from Streptomyces exfoliatus in complex with the product, 1-(2-hydroxypropyl)-2-methyl-carbazole-3,4-dione

spinqualitylabelsall models 6ipw, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ipw is a 4 chain structure with sequence from Streptomyces exfoliatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: AO6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A5A4PV77_STREX Publication Abstract from PubMed 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 alpha-hydroxyl-beta-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. An Unprecedented Cyclization Mechanism in the Biosynthesis of Carbazole Alkaloids in Streptomyces.,Kobayashi M, Tomita T, Shin-Ya K, Nishiyama M, Kuzuyama T Angew Chem Int Ed Engl. 2019 Sep 16;58(38):13349-13353. doi:, 10.1002/anie.201906864. Epub 2019 Aug 13. PMID:31350791 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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