Calcium activation mechanism of a noncanonical aromatic L-amino acid decarboxylase from psilocybin mushroom Psilocybe cubensis
Communications Biology February 26, 2026 Tianjie Li, Erin. E. Reynolds, Ziqi Wang et al.
A fungal enzyme called PcncAAAD, which decarboxylates aromatic amino acids, is activated by calcium through two metal-binding sites. The primary activation site (site A) lies between the N-terminal domain and a unique C-terminal appendage; binding calcium there stabilizes a 'lid-rim' structure that preserves the substrate-binding pocket. A secondary site (site B) within the C-terminal domain helps stabilize the enzyme's overall structure. Computer simulations and lab tests show that disrupting site A or the lid-rim severely distorts the active site and reduces or eliminates activity. Sodium does not activate the enzyme. The work clarifies how calcium activates this enzyme and may guide engineering of similar enzymes for making aromatic amino acid derivatives.