Calcium Activation Mechanism of a Noncanonical Aromatic L-Amino Acid Decarboxylase from Psilocybin Mushroom
Research Square April 28, 2025 Yi Wang, Tianjie Li, Erin S. Reynolds et al.
An enzyme called PcncAAAD, a noncanonical aromatic L-amino acid decarboxylase, is activated by calcium through a specific mechanism. Using computer simulations and lab experiments, researchers identified two calcium-binding sites: site A, at the junction of two enzyme domains, primarily drives activation, while site B within a unique tail domain stabilizes the enzyme's structure. Calcium binding at site A stabilizes a 'lid-rim' structure that maintains the substrate-binding pocket. Mutations disrupting site A or this lid-rim severely distort the active site and reduce or eliminate enzyme activity. These findings clarify how calcium activates this enzyme and may aid in designing enzymes to produce aromatic amino acid derivatives.