8qxq

PsiM in complex with SAH and psilocybin

spinqualitylabelsall models 8qxq, resolution 0.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8qxq is a 1 chain structure with sequence from Psilocybe cubensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 0.94Å Ligands: CL, SAH, X8Q Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 A) 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. Methyl transfer in psilocybin biosynthesis.,Hudspeth J, Rogge K, Dorner S, Mull M, Hoffmeister D, Rupp B, Werten S Nat Commun. 2024 Mar 28;15(1):2709. doi: 10.1038/s41467-024-46997-z. PMID:38548735 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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