8ZII

Crystal structure of the methyltransferase PsiM in complex with SAH and Norbaeocystin

8ZII の概要

• エントリーDOI: 10.2210/pdb8zii/pdb
• 分子名称: Psilocybin synthase, S-ADENOSYL-L-HOMOCYSTEINE, Norbaeocystin, ... (4 entities in total)
• 機能のキーワード: norbaeocystin, baeocystin, psilocybin, methyltransferase, sam, sah, transferase
• 由来する生物種: Psilocybe cubensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35193.74

構造登録者

Meng, C.Y.,Wen, Y.,Guo, W.T.,Wu, B.X. (登録日: 2024-05-14, 公開日: 2025-04-02)

主引用文献

Meng, C.,Guo, W.,Xiao, C.,Wen, Y.,Zhu, X.,Zhang, Q.,Liang, Y.,Li, H.,Xu, S.,Qiu, Y.,Chen, H.,Lin, W.J.,Wu, B.
Structural basis for psilocybin biosynthesis.
Nat Commun, 16:2827-2827, 2025

PubMed Abstract: Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to the biosynthesis of psilocybin can enhance its production process. In this study, we elucidate the crystal structures of L-tryptophan-specific decarboxylase PsiD in both its apo and tryptamine-bound states, the 4-hydroxytryptamine kinase PsiK bound to its substrate, and several forms of the methyltransferase PsiM in either apo or substrate-bound forms derived from the psychedelic mushroom. Structure-based evaluations reveal the mechanisms of self-cleavage and self-inhibition in PsiD, along with the sequential catalytic steps from 4-hydroxytryptamine to the final compound, psilocybin. Additionally, we showcase the antidepressant properties of biosynthetic intermediates of psilocybin on female mice experiencing depression-like behaviors induced by sub-chronic variable stress. Our studies establish a structural basis for the future biosynthetic production of psilocybin using these enzymes and emphasize the clinical potential of norbaeocystin.

PubMed: 40121242
DOI: 10.1038/s41467-025-58239-x

実験手法

X-RAY DIFFRACTION (2.5 Å)