8JMQ

Crystal structure of hinokiresinol synthase

Summary for 8JMQ

• Entry DOI: 10.2210/pdb8jmq/pdb
• Descriptor: Hinokiresinol synthase beta subunit, Hinokiresinol synthase alpha subunit (3 entities in total)
• Functional Keywords: hinokiresinol, hinokiresinol synthase, biosynthetic protein
• Biological source: Asparagus officinalis (garden asparagus); More
• Total number of polymer chains: 2
• Total formula weight: 42388.83

Authors

Ding, Y.,Ushimaru, R.,Mori, T.,Abe, I. (deposition date: 2023-06-05, release date: 2023-12-20, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)