7P4O

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

Summary for 7P4O

• Entry DOI: 10.2210/pdb7p4o/pdb
• Descriptor: 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)
• Functional Keywords: 9(r)-delta6a, 10a-thc, inhibitor, hydrolase
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 1
• Total formula weight: 98175.28

Authors

Eymery, M.C.,McCarthy, A.A.,Hausmann, J. (deposition date: 2021-07-12, release date: 2022-12-28, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.69 Å)