Academic journal article Journal of Environmental Health

Enzyme Structure Has Implications for Defense against Chemical Weapons. (EH Update)

Academic journal article Journal of Environmental Health

Enzyme Structure Has Implications for Defense against Chemical Weapons. (EH Update)

Article excerpt

A report in the journal Nature Structural Biology offers the first molecular explanation of how the body metabolizes and detoxifies cocaine and heroin. This work, whose lead author is Sompop Bencharit, a graduate student in the laboratory of Dr. Matthew R. Redimbo of the University of North Carolina at Chapel Hill, also suggests a system that can be engineered to detoxify chemical weapons, including sarin, soman, tabun, and VX gases.

The report, which received advance online publication on April 7, presents the first crystal structure of the protein human car-boxylesterase 1, or hCE1. This protein, an enzyme, is a broad-spectrum bioscavenger found throughout the body--in the liver, small intestine, kidney, lungs, testes, and scavenger cells. It also circulates to a lesser extent in human blood plasma. The report describes how hCE1 is responsible for metabolizing the first step of cocaine breakdown in the body and the first two steps of heroin breakdown. The researchers determined the crystal structure of the enzyme in complexes with analogues of cocaine and heroin. They found that the enzyme could bind to two cocaine molecules simultaneously, but that it specifically generates the primary metabolic breakdown product (metabolite) of cocaine. This finding, the report concludes, indicates that the enzyme holds "significant promise in the treatment of acute cocaine overdose. …

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