8JMR

Crystal structure of hinokiresinol synthase in complex with 1,7-bis(4-hydroxyphenyl)hepta-1,6-dien-3-one

8JMR の概要

• エントリーDOI: 10.2210/pdb8jmr/pdb
• 分子名称: Hinokiresinol synthase alpha subunit, Hinokiresinol synthase beta subunit, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hinokiresinol, hinokiresinol synthase, biosynthetic protein
• 由来する生物種: Asparagus officinalis (garden asparagus); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42779.23

構造登録者

Ding, Y.,Ushimaru, R.,Mori, T.,Abe, I. (登録日: 2023-06-05, 公開日: 2023-12-20, 最終更新日: 2024-10-16)

主引用文献

Ushimaru, R.,Ding, Y.,Mori, T.,Miyamoto, K.,Uchiyama, M.,Abe, I.
Structural and Mechanistic Insights into the C-C Bond-Forming Rearrangement Reaction Catalyzed by Heterodimeric Hinokiresinol Synthase.
J.Am.Chem.Soc., 145:21966-21973, 2023

PubMed Abstract: Hinokiresinol synthase (HRS) from consists of two subunits, α and β, and catalyzes an unusual decarboxylative rearrangement reaction of 4-coumaryl 4-coumarate to generate ()-hinokiresinol with complete stereoselectivity. Herein, we describe the mechanism of rearrangement catalysis and the role played by the heterodimeric HRS, through structural and computational analyses. Our results suggest that the HRS reaction is unlikely to proceed via the previously hypothesized Claisen rearrangement mechanism. Instead, we propose that the 4-coumaryl 4-coumarate substrate is first cleaved into coumarate and an extended -quinone methide, which then recombine to generate a new C-C bond. These processes are facilitated by proton transfers mediated by the basic residues (α-Lys164, α-Arg169, β-Lys168, and β-Arg173) in the cavity at the heterodimer interface. The active site residues, α-Asp165, β-Asp169, β-Trp17, β-Met136, and β-Ala171, play crucial roles in controlling the regioselectivity of the coupling between the fragmented intermediates as well as the stereoselectivity of the decarboxylation step, leading to the formation of the ()-hinokiresinol product.

PubMed: 37729620
DOI: 10.1021/jacs.3c06762

実験手法

X-RAY DIFFRACTION (2.2 Å)