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Structure of pain-modulating enzyme described by scientists at the Scripps Research Institute

A group of researchers from The Scripps Research Institute (TSRI) have solved the structure of an enzyme that modulates central nervous system (CNS) functions such as pain perception, cognition, feeding, sleep, and locomotor activity.

The enzyme, described in the latest issue of the journal Science, is called fatty acid amide hydrolase (FAAH), and it breaks down certain fatty signaling molecules that reside in the lipid membranes of CNS cells. The TSRI group reports that FAAH modulates the action of these fatty signaling molecules through an unusual mechanism of action whereby it scoops them out of the cell membranes and chews them up.

"I envision that if someone could make a specific inhibitor to FAAH, you could, in principal, get pain relief without any of the side effects," says Benjamin Cravatt, one of the paper's lead authors and an investigator in TSRI's Department of Cell Biology, Department of Chemistry, and The Skaggs Institute for Chemical Biology.

"As soon as we had the view of the active site, we knew FAAH could be used to make lead clinical candidates," adds Raymond Stevens, who is a professor in the Department of Molecular Biology and Chemistry at TSRI and the other lead author on the paper. "The deep pocket with well-defined cavities provides the guidance to take the currently available tight binding inhibitors and improve on their specificity and pharmakokinetic properties."

Pain Management and FAAH

Easing pain is practically synonymous with practicing medicine, and since before the days of Hippocrates, doctors have sought the best ways of doing this--looking for compounds that not only ease pain, but do so as fast, effectively, and lastingly as possible--and without any unwanted side effects.

Every analgesic, from opiates to hypnotism to electroshocks to balms, have side effects, and therein lies the rub: whether relieving the pain or the side effects is more pressing.

One compound that
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Contact: Jason Bardi
jasonb@scripps.edu
858-784-9254
Scripps Research Institute
28-Nov-2002


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