8X4S

The L-tryptophan specific decarboxylase PsiD covalent bonding with tryptamine

This is a non-PDB format compatible entry.

Summary for 8X4S

• Entry DOI: 10.2210/pdb8x4s/pdb
• Descriptor: L-tryptophan decarboxylase, (2~{R})-2-[2-(1~{H}-indol-3-yl)ethylamino]propanoic acid, ... (4 entities in total)
• Functional Keywords: decarboxylase, psilocybin, l-tryptophan, psilocin, tryptamine, oxidoreductase
• Biological source: Psilocybe cubensis; More
• Total number of polymer chains: 12
• Total formula weight: 299209.54

Authors

Meng, C.Y.,Wen, Y.,Guo, W.T.,Wu, B.X. (deposition date: 2023-11-15, release date: 2024-11-20, Last modification date: 2025-04-02)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)