8PB3

PsiM in complex with SAH and norbaeocystin, monoclinic crystal form

PDB DOI: https://doi.org/10.2210/pdb8PB3/pdb

Classification: TRANSFERASE
Organism(s): Psilocybe cubensis
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2023-06-08 Released: 2024-04-03
Deposition Author(s): Werten, S., Hudspeth, J., Rupp, B.
Funding Organization(s): Austrian Science Fund

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.18 ?
R-Value Free: 0.196
R-Value Work: 0.183
R-Value Observed: 0.183

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Methyl transfer in psilocybin biosynthesis.

Hudspeth, J., Rogge, K., Dorner, S., Mull, M., Hoffmeister, D., Rupp, B., Werten, S.

(2024) Nat Commun 15: 2709-2709

PubMed: 38548735 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41467-024-46997-z
Primary Citation of Related Structures:
8PB3, 8PB4, 8PB5, 8PB6, 8PB7, 8PB8, 8QXQ

PubMed Abstract:
Psilocybin, the natural hallucinogen produced by Psilocybe ("magic") mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolution (0.9??) crystal structures of PsiM trapped at various stages of its reaction cycle, providing detailed insight into the SAM-dependent methylation mechanism. Structural and phylogenetic analyses suggest that PsiM derives from epitranscriptomic N ⁶-methyladenosine writers of the METTL16 family, which is further supported by the observation that bound substrates physicochemically mimic RNA. Inherent limitations of the ancestral monomethyltransferase scaffold hamper the efficiency of psilocybin assembly and leave PsiM incapable of catalysing trimethylation to aeruginascin. The results of our study will support bioengineering efforts aiming to create novel variants of psilocybin with improved therapeutic properties.

Organizational Affiliation

Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

Macromolecule Content

Total Structure Weight: 73.19 kDa
Atom Count: 5,799
Modelled Residue Count: 620
Deposited Residue Count: 644
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Psilocybin synthase	A, B	322	Psilocybe cubensis	Mutation(s): 0 Gene Names: psiM EC: 2.1.1
UniProt
Find proteins for P0DPA9 (Psilocybe cubensis) Explore P0DPA9 Go to UniProtKB: P0DPA9
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P0DPA9
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SAH (Subject of Investigation/LOI) Query on SAH Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain I [auth B] MOL2 format, chain C [auth A] MOL2 format, chain I [auth B] mmCIF format, chain C [auth A] mmCIF format, chain I [auth B]	C [auth A], I [auth B]	S-ADENOSYL-L-HOMOCYSTEINE C₁₄ H₂₀ N₆ O₅ S ZJUKTBDSGOFHSH-WFMPWKQPSA-N		Interactions Focus chain C [auth A] Focus chain I [auth B] Interactions & Density Focus chain C [auth A] Focus chain I [auth B]
XP6 (Subject of Investigation/LOI) Query on XP6 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain J [auth B] MOL2 format, chain D [auth A] MOL2 format, chain J [auth B] mmCIF format, chain D [auth A] mmCIF format, chain J [auth B]	D [auth A], J [auth B]	Norbaeocystin C₁₀ H₁₃ N₂ O₄ P IKQGYCWFBVEAKF-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain J [auth B] Interactions & Density Focus chain D [auth A] Focus chain J [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain K [auth B] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain K [auth B] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain K [auth B]	F [auth A], G [auth A], H [auth A], K [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain K [auth B] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain K [auth B]