10EF

Cannabis sativa O-methyl transferase 1 - DHR soak

10EF の概要

• エントリーDOI: 10.2210/pdb10ef/pdb
• 分子名称: O-methyltransferase 1, GLYCEROL, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: o-methyltransferase, dihydroresveratrol, transferase
• 由来する生物種: Cannabis sativa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43936.93

構造登録者

Forrester, T.J.B.,Kimber, M.S. (登録日: 2026-01-15, 公開日: 2026-07-01)

主引用文献

Boddington, K.F.,Soubeyrand, E.,Van Gelder, K.,Perrin, C.,Forrester, T.J.B.,Holborn, J.,Casaretto, J.A.,Al-Abdul-Wahid, M.S.,Piotrowski, M.L.,Magolan, J.,Lalonde, J.,Kimber, M.S.,Rothstein, S.J.,Akhtar, T.A.
Cell-Free Synthesis of Cannabistilbene I: A Dual Acting Anti-Inflammatory from Cannabis sativa.
J.Nat.Prod., 2026

PubMed Abstract: Despite the potential of Cannabis bibenzyls to remedy acute and chronic inflammation, their relative scarcity, in planta, has hindered applications for them in mainstream therapeutic efforts. Here, we describe the biocatalytic synthesis of cannabistilbene I (), a prototypical Cannabis bibenzyl, and demonstrate its utility as an anti-inflammatory agent. A Cannabis -methyltransferase (CsOMT1) was first identified that catalyzes the 3-hydroxymethylation of dihydroresveratrol () to produce pinobistilbene (). Structural characterization of CsOMT1 revealed that the substrate-binding pocket requires the ethyl bridge on to twist with a dihedral angle of -110°, thereby explaining why less flexible aromatics such as stilbenes serve as poor enzymatic substrates. Next, a prenyltransferase (CloQ) from the Gram-positive bacterium was shown to prenylate the 3'-position of the B-ring on into . Using these two enzymes, a cell-free method was then developed to synthesize and the compound was shown to inhibit both microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase enzyme activity, in vitro, more effectively than the leading commercially available inhibitors. Together, these results establish a platform for producing cannabistilbene I () that circumvents the challenges of traditional "chemical synthesis", and which is amenable to produce similar value-added compounds that are not easily accessible from nature.

PubMed: 42139234
DOI: 10.1021/acs.jnatprod.6c00318

実験手法

X-RAY DIFFRACTION (2.25 Å)