Identifying Protein 'Pockets' that Block Hallucinogens

In a paper published in Nature, a team of scientists from the University of North Carolina and elsewhere describe the chemical structure of the kappa opioid receptor (KOR). This cell protein binds Salvinorin A, a widely-abused hallucinogen known as “magic mint,” as well as other drugs.

The research team used a variety of tools to determine KOR’s structure, including protein engineering and chemical biology. The crucial step was crystallography. In this technique, a crystal of a protein is created whose orderly structure can be more easily identified.

“It took between three and four years in a collaboration to engineer the protein and get large amounts of it, and then another year or so of trial and error to get it to crystallize,” said Dr. Bryan Roth, professor of pharmacology at North Carolina and a co-author of the paper.

“With the crystals, it took less then a month to solve the structure.”

Because the protein’s “binding pocket” is so large, there may be a variety of drugs that could alter or diminish its ability to bind.

“Basically, the larger the binding pocket, the more likely many structurally different drugs can bind to it,” Roth said.

“We’re in the process of creating new drug-like compounds, using KOR’s structural data, for use as medications.”

Since opioid receptors play a large role in causing pain, depression and addiction, the key, notes Roth, will be creating drugs that interfere with KOR reception.

“When we activate KOR in the brain, we induce hallucinations. So we want to make KOR activators which only work outside the brain.”

Activating KOR elsewhere in the body could result in suppression of depression, anxiety and other disorders.