6NBR
Crystal Structure of Piper methysticum Kavalactone Reductase 1 in complex with NADP
Summary for 6NBR
| Entry DOI | 10.2210/pdb6nbr/pdb |
| Related | 6CQB 6OP5 |
| Descriptor | Kavalactone reductase 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total) |
| Functional Keywords | phenylpropanoid pathway, kavalactone biosynthesis, transferase |
| Biological source | Piper methysticum |
| Total number of polymer chains | 4 |
| Total formula weight | 149060.86 |
| Authors | Pluskal, T.,Weng, J.K. (deposition date: 2018-12-09, release date: 2019-06-19, Last modification date: 2024-04-03) |
| Primary citation | 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 Cited by 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: 31332312DOI: 10.1038/s41477-019-0474-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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