6ebn

Crystal structure of Psilocybe cubensis noncanonical aromatic amino acid decarboxylase

spinqualitylabelsall models 6ebn, resolution 1.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ebn is a 2 chain structure with sequence from Psicu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FMT, GOL, NA NonStd Res: LLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 towards 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-beta-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. Monoamine biosynthesis via a noncanonical calcium-activatable aromatic amino acid decarboxylase in psilocybin mushroom.,Torrens-Spence MP, Liu CT, Pluskal T, Chung YK, Weng JK ACS Chem Biol. 2018 Nov 28. doi: 10.1021/acschembio.8b00821. PMID:30484626 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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