6IPW

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

6IPW の概要

• エントリーDOI: 10.2210/pdb6ipw/pdb
• 分子名称: CqsB2, 2-methyl-1-[(2R)-2-oxidanylpropyl]-9H-carbazole-3,4-dione (3 entities in total)
• 機能のキーワード: carbazole biosynthesis, polyketide aromatase/cyclase, biosynthetic protein
• 由来する生物種: Streptomyces exfoliatus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 111657.60

構造登録者

Tomita, T.,Kobayashi, M.,Nishiyama, M.,Kuzuyama, T. (登録日: 2018-11-05, 公開日: 2019-10-16, 最終更新日: 2023-11-22)

主引用文献

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

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: 31350791
DOI: 10.1002/anie.201906864

実験手法

X-RAY DIFFRACTION (2.1 Å)