6EBN

Crystal structure of Psilocybe cubensis noncanonical aromatic amino acid decarboxylase

6EBN の概要

• エントリーDOI: 10.2210/pdb6ebn/pdb
• 分子名称: non canonical aromatic amino acid decarboxylase, GLYCEROL, FORMIC ACID, ... (5 entities in total)
• 機能のキーワード: aromatic amino acid decarboxylase, metal binding protein
• 由来する生物種: Psilocybe cubensis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 228125.00

構造登録者

Torrens-Spence, M.P.,Chun-Ting, L.,Pluskal, T.,Chung, Y.K.,Weng, J.K. (登録日: 2018-08-06, 公開日: 2018-12-12, 最終更新日: 2023-11-15)

主引用文献

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

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: 30484626
DOI: 10.1021/acschembio.8b00821

実験手法

X-RAY DIFFRACTION (1.96631108321 Å)