Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.
Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.
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DOI：
10.1038/s41598-017-10571-z
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发表时间：
2017-09-05
影响因子：
4.6
通讯作者：
Mor TS
中科院分区：
文献类型：
--
作者：
Larrimore KE;Kazan IC;Kannan L;Kendle RP;Jamal T;Barcus M;Bolia A;Brimijoin S;Zhan CG;Ozkan SB;Mor TS
丁酰胆碱酯酶（BChE）是一种具有广泛底物和配体特异性的酶，可以通过结合和/或水解各种异生物质试剂和毒物（其中许多靶向中枢和外周神经系统）来发挥广义生物清除剂的作用。BChE的变体经过合理设计，以提高酶水解可卡因的精神活性对映体的能力。克隆这些变体，然后使用magnICON瞬时表达系统在植物中表达，并研究其酶性质。特别是，我们探讨了这些定点突变对BChE的各种底物的酶动力学的影响。我们进一步比较了各种抗胆碱酯酶，包括有机磷神经毒剂和杀虫剂对这些BChE变体相对于野生型酶的亲和力。除了作为可卡因成瘾相关疾病的治疗之外，增强对其他有害物质的生物清除可以增加植物来源的重组酶作为多价治疗剂的实用性和多功能性。
Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme’s ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in plants and their enzymatic properties were investigated. In particular, we explored the effects that these site-directed mutations have over the enzyme kinetics with various substrates of BChE. We further compared the affinity of various anticholinesterases including organophosphorous nerve agents and pesticides toward these BChE variants relative to the wild type enzyme. In addition to serving as a therapy for cocaine addiction-related diseases, enhanced bioscavenging against other harmful agents could add to the practicality and versatility of the plant-derived recombinant enzyme as a multivalent therapeutic.
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影响因子：
5.1
作者：
Geyer, BC;Muralidharan, M;Mor, TS
通讯作者：
Mor, TS
影响因子：
2.9
作者：
BARAK, D;ORDENTLICH, A;SHAFFERMAN, A
通讯作者：
SHAFFERMAN, A
影响因子：
4.1
作者：
Blong, RM;Bedows, E;Lockridge, O
通讯作者：
Lockridge, O
影响因子：
4.8
作者：
Evron, Tama;Geyer, Brian C.;Mor, Tsafrir S.
通讯作者：
Mor, Tsafrir S.
影响因子：
6.7
作者：
Khan, SB;Azhar-ul-Haq;Choudhary, MI
通讯作者：
Choudhary, MI