"Nature" published the molecular mechanism of antidepressant ketamine targeting human NMDA receptors

Depression affects more than 300 million people in the world .

Existing studies have shown that ketamine, as an important glutamate-gated ion channel NMDA receptor blocker in the brain , can participate in the regulation of synaptic transmission and synaptic plasticity signaling pathways by inhibiting the activity of NMDA receptor channels.

In this research, Zhu Shujia’s team focused on the two most abundant subtypes of GluN1-GluN2A and GluN1-GluN2B NMDA receptors in adult mammalian brains , and used eukaryotic cell expression systems to carry out a large number of protein expression and purification conditions in the early stage.

The electron microscopy study "see" and confirmed ketamine NMDA binding site on the receptor, and reveals GluN1-N616 hydrogen bonding and GluN2A-L642 hydrophobic interaction, ketamine stable binding NMDA channel receptors It plays a key role in the process of blocking the passage in the cavity

Doctoral students Zhang Youyi and Zhang Tongtong of the Center for Excellence in Brain Science and Intelligent Technology Innovation of the Chinese Academy of Sciences and Associate Professor Ye Fei of Zhejiang Sci-Tech University are the co-first authors of the paper.

Figure note ( A ) Cryo- electron microscopic three-dimensional structure of human GluN1-GluN2A NMDA receptor bound to ketamine