7P4O

Crystal structure of Autotaxin and 9(R)-delta6a,10a-THC

7P4O の概要

• エントリーDOI: 10.2210/pdb7p4o/pdb
• 分子名称: Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 7alpha-hydroxycholesterol, ... (10 entities in total)
• 機能のキーワード: 9(r)-delta6a, 10a-thc, inhibitor, hydrolase
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 98175.28

構造登録者

Eymery, M.C.,McCarthy, A.A.,Hausmann, J. (登録日: 2021-07-12, 公開日: 2022-12-28, 最終更新日: 2024-11-13)

主引用文献

Eymery, M.C.,McCarthy, A.A.,Hausmann, J.
Linking medicinal cannabis to autotaxin-lysophosphatidic acid signaling.
Life Sci Alliance, 6:-, 2023

PubMed Abstract: Autotaxin is primarily known for the formation of lysophosphatidic acid (LPA) from lysophosphatidylcholine. LPA is an important signaling phospholipid that can bind to six G protein-coupled receptors (LPA). The ATX-LPA signaling axis is a critical component in many physiological and pathophysiological conditions. Here, we describe a potent inhibition of Δ--tetrahydrocannabinol (THC), the main psychoactive compound of medicinal cannabis and related cannabinoids, on the catalysis of two isoforms of ATX with nanomolar apparent EC values. Furthermore, we decipher the binding interface of ATX to THC, and its derivative 9(R)-Δ6a,10a-THC (6a10aTHC), by X-ray crystallography. Cellular experiments confirm this inhibitory effect, revealing a significant reduction of internalized LPA in the presence of THC with simultaneous ATX and lysophosphatidylcholine stimulation. Our results establish a functional interaction of THC with autotaxin-LPA signaling and highlight novel aspects of medicinal cannabis therapy.

PubMed: 36623871
DOI: 10.26508/lsa.202201595

実験手法

X-RAY DIFFRACTION (1.69 Å)