ShanghaiTech Scientists Resolve the Structure of the Human "Marijuana Receptor"

SHANGHAI, Oct. 20, 2016 /PRNewswire/ -- A team of scientists led by the iHuman Institute of ShanghaiTech University has determined and analyzed the high-resolution atomic structure of human cannabinoid receptor 1 (CB(1)), also known as the "marijuana receptor". The three dimensional image of CB(1 )presented October 20(th) in Cell, could explain how pain medications meant to mimic cannabis use without the "high" can cause unintended side effects, and provide a foundation for future therapies.

"The detailed molecular structure of the receptor in complex with agonist or antagonist will help people understand how cellular signaling is affected by medicine molecules, and will offer a valuable framework for designing safer and more effective drugs", said iHuman Deputy Director and Professor Zhi-Jie Liu, one of the corresponding authors of the paper.

The 3D images reveal how molecules like THC bind to CB(1), which is found embedded in the surface of many nerve cells. "Researchers are fascinated by how you can make changes in THC or synthetic cannabinoids and have such different effects," says iHuman Founding Director and Professor Raymond Stevens, co-leader of the study, "Now that we finally have the structure of CB(1), we can start to understand how these changes to the drug structure can affect the receptor."

The first author of this study, Tian Hua, a graduate student at Prof. Zhi-Jie Liu's lab, and her colleagues determined the crystal structure of CB(1) in complex with AM6538 at 2.8 A resolution. AM6538, synthesized by the second author Kiran Vemuri from Northeastern University, USA, is expected to have a long half-life and be potentially useful in the treatment of addiction disorders. Additionally, their studies found a number of structurally dissimilar CB(1) ligands can be accommodated when docked into the binding domain defined by the CB(1) crystal structure. This should allow a diverse set of CB(1) ligands to interact with CB(1) through different binding motifs and have distinct pharmacological profiles.

Author Contact:

Zhi-Jie Liu, PhDProfessor, iHuman InstituteShanghaiTech []

Media Contacts:

Xun Liu, PhDPress Officer, ShanghaiTech [] Phone: +86-21-2068-5159

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