作者
Liu Xue, Shurong Hou, Min Tong, Lei Fang, Xiabin Chen, Zhenyu Jin, Hsin-Hsiung Tai, Fang Zheng, Chang-Guo Zhan
发表日期
2013/8/1
期刊
Biochemical Journal
卷号
453
期号
3
页码范围
447-454
出版商
Portland Press Ltd.
简介
Cocaine is a widely abused drug without an FDA (Food and Drug Administration)-approved medication. It has been recognized that an ideal anti-cocaine medication would accelerate cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e. human BChE (butyrylcholinesterase)-catalysed hydrolysis. However, the native human BChE has a low catalytic activity against cocaine. We recently designed and discovered a BChE mutant (A199S/F227A/S287G/A328W/Y332G) with a high catalytic activity (kcat=5700 min−1, Km=3.1 μM) specifically for cocaine, and the mutant was proven effective in protecting mice from acute cocaine toxicity of a lethal dose of cocaine (180 mg/kg of body weight, LD100). Further characterization in animal models requires establishment of a high-efficiency stable cell line for the BChE mutant production at a relatively …
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