A highly efficient cocaine-detoxifying enzyme obtained by computational design.
A highly efficient cocaine-detoxifying enzyme obtained by computational design.
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DOI：
10.1038/ncomms4457
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发表时间：
2014-03-18
影响因子：
16.6
通讯作者：
Zhan, Chang-Guo
中科院分区：
文献类型：
--
作者：
Zheng, Fang;Xue, Liu;Hou, Shurong;Liu, Junjun;Zhan, Max;Yang, Wenchao;Zhan, Chang-Guo
与天然存在的酶相比，计算设计的酶通常效率低得多，其催化活性比扩散极限低六个数量级以上。在这里，我们使用两步计算设计方法，结合实验工作，设计一个高效的可卡因水解酶。我们从人丁酰胆碱酯酶（BChE），这是特异性的可卡因水解工程E30-6，并获得一个更高的催化效率可卡因转化比天然BChE底物，乙酰胆碱（ACh）的转换。E30-6对可卡因水解的催化效率与已知最有效的天然存在的水解酶乙酰胆碱酯酶的催化效率相当，其催化活性接近扩散极限。我们进一步表明，E30-6可以保护小鼠免受随后给予的致死剂量的可卡因，这表明该酶可能在可卡因解毒或可卡因滥用的背景下具有治疗潜力。
Compared to naturally occurring enzymes, computationally designed enzymes are usually much less efficient, with their catalytic activities being more than six orders of magnitude below the diffusion limit. Here we use a two-step computational design approach, combined with experimental work, to design a highly efficient cocaine hydrolising enzyme. We engineer E30-6 from human butyrylcholinesterase (BChE), which is specific for cocaine hydrolysis, and obtain a much higher catalytic efficiency for cocaine conversion than for conversion of the natural BChE substrate, acetylcholine (ACh). The catalytic efficiency of E30-6 for cocaine hydrolysis is comparable to that of the most efficient known naturally-occurring hydrolytic enzyme, acetylcholinesterase, the catalytic activity of which approaches the diffusion limit. We further show that E30-6 can protect mice from a subsequently administered lethal dose of cocaine, suggesting the enzyme may have therapeutic potential in the setting of cocaine detoxification or cocaine abuse.
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影响因子：
2
作者：
Ilyushin, D. G.;Haertley, O. M.;Ponomarenko, N. A.
通讯作者：
Ponomarenko, N. A.
影响因子：
3.6
作者：
Gao, Y;Atanasova, E;Brimijoin, S
通讯作者：
Brimijoin, S
影响因子：
3.3
作者：
Gao, DQ;Zhan, CG
通讯作者：
Zhan, CG
影响因子：
3.6
作者：
Gao, Daquan;Narasimhan, Diwahar L.;Zhan, Chang-Guo
通讯作者：
Zhan, Chang-Guo
影响因子：
8
作者：
Althoff, Eric A.;Wang, Ling;Jiang, Lin;Giger, Lars;Lassila, Jonathan K.;Wang, Zhizhi;Smith, Matthew;Hari, Sanjay;Kast, Peter;Herschlag, Daniel;Hilvert, Donald;Baker, David
通讯作者：
Baker, David