6EBN
Crystal structure of Psilocybe cubensis noncanonical aromatic amino acid decarboxylase
Summary for 6EBN
| Entry DOI | 10.2210/pdb6ebn/pdb |
| Descriptor | non canonical aromatic amino acid decarboxylase, GLYCEROL, FORMIC ACID, ... (5 entities in total) |
| Functional Keywords | aromatic amino acid decarboxylase, metal binding protein |
| Biological source | Psilocybe cubensis |
| Total number of polymer chains | 2 |
| Total formula weight | 228125.00 |
| Authors | Torrens-Spence, M.P.,Chun-Ting, L.,Pluskal, T.,Chung, Y.K.,Weng, J.K. (deposition date: 2018-08-06, release date: 2018-12-12, Last modification date: 2023-11-15) |
| Primary citation | Torrens-Spence, M.P.,Liu, C.T.,Pluskal, T.,Chung, Y.K.,Weng, J.K. Monoamine Biosynthesis via a Noncanonical Calcium-Activatable Aromatic Amino Acid Decarboxylase in Psilocybin Mushroom. ACS Chem. Biol., 13:3343-3353, 2018 Cited by PubMed Abstract: Aromatic l-amino acid decarboxylases (AAADs) are a phylogenetically diverse group of enzymes responsible for the decarboxylation of aromatic amino acid substrates into their corresponding aromatic arylalkylamines. AAADs have been extensively studied in mammals and plants as they catalyze the first step in the production of neurotransmitters and bioactive phytochemicals, respectively. Unlike mammals and plants, the hallucinogenic psilocybin mushroom Psilocybe cubensis reportedly employs an unrelated phosphatidylserine-decarboxylase-like enzyme to catalyze l-tryptophan decarboxylation, the first step in psilocybin biosynthesis. To explore the origin of this chemistry in psilocybin mushroom, we generated the first de novo transcriptomes of P. cubensis and investigated several putative l-tryptophan-decarboxylase-like enzymes. We report the biochemical characterization of a noncanonical AAAD from P. cubensis ( PcncAAAD) that exhibits substrate permissiveness toward l-phenylalanine, l-tyrosine, and l-tryptophan, as well as chloro-tryptophan derivatives. The crystal structure of PcncAAAD revealed the presence of a unique C-terminal appendage domain featuring a novel double-β-barrel fold. This domain is required for PcncAAAD activity and regulates catalytic rate and thermal stability through calcium binding. PcncAAAD likely plays a role in psilocybin production in P. cubensis and offers a new tool for metabolic engineering of aromatic-amino-acid-derived natural products. PubMed: 30484626DOI: 10.1021/acschembio.8b00821 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.96631108321 Å) |
Structure validation
Download full validation report
