SSRL has played an important role in characterizing a family of enzymes that detoxify heroin and cocaine, and have the potential to metabolically eliminate the nerve poisons sarin, soman, and tabun, which have claimed thousands of lives. Using x-ray crystallographic data, the Redinbo group at the University of North Carolina at Chapel Hill has uncovered the specific and general ways the carboxylesterase enzymes bind to those dangerous substances. This new understanding of the structure-function relationships will be of very significant value in designing drugs to combat overdoses, terrorist attacks and chemical warfare. Redinbo's group is working on developing more specific and faster versions of the human form of the enzyme (hCE1) to inject into people who have overdosed on heroin and cocaine and into soldiers potentially facing nerve gas attacks.

Carboxylesterases in mammals are responsible for breaking down a wide variety of human-made drugs and foreign chemicals, and may have evolved to safely process the chemicals many plants use to protect themselves. The first crystallographic study of hCE1 bound to cocaine- and heroin-like compounds revealed important molecular details about how the drugs are metabolized and how the enzyme can recognize such structurally diverse compounds. Redinbo's group found that the hCE1 active site contains both a specific compartment (that binds with specific features of a compound, the way Lego pieces fit together), and a promiscuous compartment (that can bind with many shapes, the way gum sticks to many surfaces). These features enable the enzyme to act on structurally distinct chemicals like dangerous narcotics and weaponized nerve agents.