6NBR

Crystal Structure of Piper methysticum Kavalactone Reductase 1 in complex with NADP

6NBR の概要

• エントリーDOI: 10.2210/pdb6nbr/pdb
• 関連するPDBエントリー: 6CQB 6OP5
• 分子名称: Kavalactone reductase 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: phenylpropanoid pathway, kavalactone biosynthesis, transferase
• 由来する生物種: Piper methysticum
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 149060.86

構造登録者

Pluskal, T.,Weng, J.K. (登録日: 2018-12-09, 公開日: 2019-06-19, 最終更新日: 2024-04-03)

主引用文献

Pluskal, T.,Torrens-Spence, M.P.,Fallon, T.R.,De Abreu, A.,Shi, C.H.,Weng, J.K.
The biosynthetic origin of psychoactive kavalactones in kava.
Nat.Plants, 5:867-878, 2019

PubMed Abstract: Kava (Piper methysticum) is an ethnomedicinal shrub native to the Polynesian islands with well-established anxiolytic and analgesic properties. Its main psychoactive principles, kavalactones, form a unique class of polyketides that interact with the human central nervous system through mechanisms distinct from those of conventional psychiatric drugs. However, an unknown biosynthetic machinery and difficulty in chemical synthesis hinder the therapeutic use of kavalactones. In addition, kava also produces flavokavains, which are chalconoids with anticancer properties structurally related to kavalactones. Here, we report de novo elucidation of the key enzymes of the kavalactone and flavokavain biosynthetic network. We present the structural basis for the evolutionary development of a pair of paralogous styrylpyrone synthases that establish the kavalactone scaffold and the catalytic mechanism of a regio- and stereo-specific kavalactone reductase that produces a subset of chiral kavalactones. We further demonstrate the feasibility of engineering styrylpyrone production in heterologous hosts, thus opening a way to develop kavalactone-based non-addictive psychiatric therapeutics through synthetic biology.

PubMed: 31332312
DOI: 10.1038/s41477-019-0474-0

実験手法

X-RAY DIFFRACTION (2.8 Å)