8DQQ

Crystal structure of Arabidopsis thaliana COSY in complex with scopoletin

8DQQ の概要

• エントリーDOI: 10.2210/pdb8dqq/pdb
• 分子名称: Coumarin Synthase, 7-hydroxy-2H-chromen-2-one, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: coumarin synthase, trans/cis isomerase, bahd acyltransferase, plant protein
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99765.85

構造登録者

Kim, C.Y.,Mitchell, A.J.,Gutierrez, M.,Weng, J.K. (登録日: 2022-07-19, 公開日: 2023-01-11, 最終更新日: 2023-10-25)

主引用文献

Kim, C.Y.,Mitchell, A.J.,Kastner, D.W.,Albright, C.E.,Gutierrez, M.A.,Glinkerman, C.M.,Kulik, H.J.,Weng, J.K.
Emergence of a proton exchange-based isomerization and lactonization mechanism in the plant coumarin synthase COSY.
Nat Commun, 14:597-597, 2023

PubMed Abstract: Plants contain rapidly evolving specialized enzymes that support the biosynthesis of functionally diverse natural products. In coumarin biosynthesis, a BAHD acyltransferase-family enzyme COSY was recently discovered to accelerate coumarin formation as the only known BAHD enzyme to catalyze an intramolecular acyl transfer reaction. Here we investigate the structural and mechanistic basis for COSY's coumarin synthase activity. Our structural analyses reveal an unconventional active-site configuration adapted to COSY's specialized activity. Through mutagenesis studies and deuterium exchange experiments, we identify a unique proton exchange mechanism at the α-carbon of the o-hydroxylated trans-hydroxycinnamoyl-CoA substrates during the catalytic cycle of COSY. Quantum mechanical cluster modeling and molecular dynamics further support this key mechanism for lowering the activation energy of the rate-limiting trans-to-cis isomerization step in coumarin production. This study unveils an unconventional catalytic mechanism mediated by a BAHD-family enzyme, and sheds light on COSY's evolutionary origin and its recruitment to coumarin biosynthesis in eudicots.

PubMed: 36737607
DOI: 10.1038/s41467-023-36299-1

実験手法

X-RAY DIFFRACTION (2.33 Å)