9k48
Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51K
Structural highlights
FunctionCOCE_RHOSM Hydrolyzes cocaine to benzoate and ecgonine methyl ester, endowing the bacteria with the ability to utilize cocaine as a sole source of carbon and energy for growth, as this bacterium lives in the rhizosphere of coca plants. Also efficiently hydrolyzes cocaethylene, a more potent cocaine metabolite that has been observed in patients who concurrently abuse cocaine and alcohol. Is able to prevent cocaine-induced convulsions and lethality in rat.[1] [2] [3] Publication Abstract from PubMedEnzyme therapy for cocaine detoxification should break down both cocaine and its primary toxic metabolite, benzoylecgonine (BZE), which is also the main form of cocaine contaminant in the environment. An ideal BZE-metabolizing enzyme (BZEase) is expected to be highly efficient and selective in BZE hydrolysis. Here, BZEase4 was engineered from bacterial cocaine esterase (CocE) by our reactant state-based enzyme design theories (RED), which has a 34,977-fold improved substrate discrimination between BZE and the neurotransmitter acetylcholine (ACh), compared with wild-type CocE. Under the physiological concentrations of BZE and ACh, the reaction velocity of BZEase4 against BZE is 2.25 x 10(6)-fold higher than it against ACh, suggesting BZEase4 has extremely high substrate selectivity for BZE over ACh to minimize the potential cholinergic side-effects. This study provides additional evidence supporting the further development of BZEase4 toward a promising therapeutic for cocaine overdose, a potentially effective and eco-friendly enzymatic method for BZE degradation in the environment. Catalytic mechanism, computational design, and crystal structure of a highly specific and efficient benzoylecgonine hydrolase.,Chen X, Zhang Y, Tong J, Ouyang P, Deng X, Zhang J, Liu H, Hu Y, Yao W, Wang J, Wang X, Hou S, Yao J Int J Biol Macromol. 2024 Dec;283(Pt 3):137767. doi: , 10.1016/j.ijbiomac.2024.137767. Epub 2024 Nov 17. PMID:39561846[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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