7KPT

Crystal structure of CtdE in complex with FAD and substrate 4

7KPT の概要

• エントリーDOI: 10.2210/pdb7kpt/pdb
• 関連するPDBエントリー: 7KPQ
• 分子名称: FAD-dependent monooxygenase CtdE, FLAVIN-ADENINE DINUCLEOTIDE, (6aR,7aS,11S,13aS)-6,6,11-trimethyl-4-(3-methylbut-2-en-1-yl)-6,6a,7,8,9,10,11,14-octahydro-5H,13H-13a,7a-(epiminomethano)quinolizino[2,3-b]carbazol-16-one, ... (6 entities in total)
• 機能のキーワード: fad monooxygenase, biosynthetic protein
• 由来する生物種: Penicillium citrinum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51101.11

構造登録者

Zhao, B.,Hu, L. (登録日: 2020-11-12, 公開日: 2021-06-16, 最終更新日: 2023-10-18)

主引用文献

Liu, Z.,Zhao, F.,Zhao, B.,Yang, J.,Ferrara, J.,Sankaran, B.,Venkataram Prasad, B.V.,Kundu, B.B.,Phillips Jr., G.N.,Gao, Y.,Hu, L.,Zhu, T.,Gao, X.
Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins.
Nat Commun, 12:4158-4158, 2021

PubMed Abstract: Prenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible β-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.

PubMed: 34230497
DOI: 10.1038/s41467-021-24421-0

実験手法

X-RAY DIFFRACTION (1.91 Å)