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Structural and Mechanistic Insights into the C-C Bond-Forming Rearrangement Reaction Catalyzed by Heterodimeric Hinokiresinol Synthase.
Ushimaru, Richiro; Ding, Yiling; Mori, Takahiro; Miyamoto, Kazunori; Uchiyama, Masanobu; Abe, Ikuro.
Afiliação
  • Ushimaru R; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
  • Ding Y; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan.
  • Mori T; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
  • Miyamoto K; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
  • Uchiyama M; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan.
  • Abe I; PRESTO, Japan Science and Technology Agency, Kawaguchi 332-0012, Saitama, Japan.
J Am Chem Soc ; 145(40): 21966-21973, 2023 Oct 11.
Article em En | MEDLINE | ID: mdl-37729620
Hinokiresinol synthase (HRS) from Asparagus officinalis consists of two subunits, α and ß, and catalyzes an unusual decarboxylative rearrangement reaction of 4-coumaryl 4-coumarate to generate (Z)-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 p-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, ß-Lys168, and ß-Arg173) in the cavity at the heterodimer interface. The active site residues, α-Asp165, ß-Asp169, ß-Trp17, ß-Met136, and ß-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 (Z)-hinokiresinol product.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Am Chem Soc Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Am Chem Soc Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Japão