A computationally optimised enzyme that inactivates cocaine at a speed rivalling that of the fastest enzymes found in nature has been reported in Nature Communications this week. The study suggests this artificial variant could potentially be used for cocaine detoxification.
The enzyme butyrylcholesterase (BChE) can bind and metabolise a variety of molecules, including cocaine. However, the chemical inactivation of cocaine by BChE is rather slow. Chang-Guo Zhan and colleagues used computational methods to predict a series of mutations in BChE that increase the enzyme’s speed of cocaine conversion. These alterations push the enzyme’s catalytic speed into the region of acetylcholinesterase, one of the fastest known enzymes in nature. The group further shows that their optimised BChE variant increases the survival of rats if administered intravenously shortly before a lethal cocaine injection, suggesting that the enzyme may have therapeutic potential in the setting of cocaine detoxification. However, whether BChE would still have a therapeutic effect if administered after a high dose of cocaine remains to be demonstrated.