Crystal Structures Explain Action of Bioscavenger Enzyme

The study, published April 7, 2003, in the online edition of Nature Structural Biology, revealed how humans initiate the breakdown of both narcotics and organophosphates. Investigators at the University of North Carolina (Chapel Hill, USA) employed the cocaine analog homatropine and the heroin analog naloxone to generate crystal structures of the hCE1 glycoprotein in complex with substrate molecules. They found that a selective surface ligand-binding site regulated the trimer-hexamer equilibrium of hCE1 and allowed each hCE1 monomer to bind two narcotic molecules simultaneously.

Senior author Dr. Matthew Redinbo, assistant professor in the department of chemistry at the University of North Carolina, said that the U.S. military is aggressively seeking to develop hCE1 as a battlefield reagent that could be used to detoxify sarin, soman, tabun, and VX gases. "Without the crystal structure, they have been making educated guesses as to where to make changes in the enzyme that would increase its efficiency in detoxifying these agents,” explained Dr. Redinbo. "Now, knowledge of the crystal structure takes much of the guesswork out of identifying the most effective modifications.”