Novel Human Butyrylcholinesterase Variants: Toward Organophosphonate Detoxication

Mary Dwyer; Sacha Javor; Daniel A. Ryan; Emily M. Smith; Beilin Wang; Jun Zhang; John R. Cashman

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Novel Human Butyrylcholinesterase Variants: Toward Organophosphonate Detoxication

机译：新型人类丁酰胆碱酯酶变体：走向有机膦酸盐脱毒

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Human butyrylcholinesterase (hBChE) is currently being developed as a detoxication enzyme for stoichiometric binding and/or catalytic hydrolysis of organophosphates. Herein, we describe the use of a molecular evolution method to develop novel hBChE variants with increased resistance to stereochemically defined nerve agent model compounds of soman, sarin, and cyclosarin. Novel hBChE variants (Y332S, D340H, and Y332S/D340H) were identified with an increased resistance to nerve agent model compounds that retained robust intrinsic catalytic efficiency. Molecular dynamics simulations of these variants revealed insights into the mechanism by which these structural changes conferred nerve agent model compound resistance.

机译：人丁酰胆碱酯酶（hBChE）目前正被开发为一种脱毒酶，用于化学计量结合和/或催化水解有机磷酸酯。在这里，我们描述了使用分子进化方法来开发新型的hBChE变异体，其对梭曼，沙林和环沙林的立体化学定义的神经药模型化合物具有更高的抗性。鉴定出新的hBChE变体（Y332S，D340H和Y332S / D340H）对神经药模型化合物的抗性增强，并保留了强大的固有催化效率。这些变体的分子动力学模拟揭示了对这些结构变化赋予神经毒剂模型复合抗性的机理的见解。

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《Biochemistry》 |2014年第27期|共12页
作者
Mary Dwyer; Sacha Javor; Daniel A. Ryan; Emily M. Smith; Beilin Wang; Jun Zhang; John R. Cashman;
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正文语种 eng
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Novel Human; Butyrylcholinesterase Variants; Organophosphonate Detoxication;

机译：新型人类;丁酰胆碱酯酶变体;有机膦酸盐脱毒;

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1. Novel Human Butyrylcholinesterase Variants: Toward Organophosphonate Detoxication [J] . Mary Dwyer, Sacha Javor, Daniel A. Ryan, Biochemistry . 2014,第27期

机译：新型人类丁酰胆碱酯酶变体：走向有机膦酸盐脱毒
2. In vitro detoxication of microcystins in human samples: variability among variants with different hydrophilicity and structure [J] . Santori Nicoletta, Buratti Franca Maria, Scardala Simona, Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research . 2020,第期

机译：在人样品中的微囊藻毒素的体外解毒：不同亲水性和结构的变体之间的变异性
3. Sensitivity of butyrylcholinesterase knockout mice to (--)-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimer's disease drugs and indicates butyrylcholinesterase function in neurotransmiss [J] . Duysen EG, Li B, Darvesh S, Toxicology: An International Journal Concerned with the Effects of Chemicals on Living Systems . 2007,第1a3期

机译：丁酰胆碱酯酶敲除小鼠对（-）-石杉碱甲和多奈哌齐的敏感性表明，丁酰胆碱酯酶缺乏症的人可能无法耐受这些阿尔茨海默氏病药物，并表明丁酰胆碱酯酶在神经传递中的功能
4. Mass Analyzer Comparison for Quantitative and Confirmative Determination of OPNA Biomarker Butyrylcholinesterase Peptides from Human Serum [C] . Caroline M. Watson American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2013

机译：人血清中OPNA生物标志物丁酰基苯甲酸丁二苯甲酸丁基苯甲酸酯酶肽的定量和确认测定的质谱比较
5. Bioprocess Engineering Approaches for Production and Purification of Recombinant Plant Made Human Butyrylcholinesterase [D] . Alkanaimsh, Salem. 2017

机译：用于生产和纯化重组人丁酰胆碱酯酶的生物工艺工程方法
6. Novel Human Butyrylcholinesterase Variants: TowardOrganophosphonate Detoxication [O] . Mary Dwyer, Sacha Javor, DanielA. Ryan, -1

机译：新型人类丁酰胆碱酯酶变体：向有机膦酸盐解毒
7. His-tag truncated butyrylcholinesterase as a useful construct for in vitro characterization of wild-type and variant butyrylcholinesterases [O] . Erik C. Ralph, Longkuan Xiang, John R. Cashman, 2011

机译：His-标签截短的丁酰胆碱酯酶作为野生型和变体丁酰胆碱酯酶的体外表征的有用构建体
8. Recombinant Human Butyrylcholinesterase G390V, the Fluoride-2 Variant, Expressedin Chinese Hamster Ovary Cells, Is a Low Affinity Variant [R] . Masson, P., Adkins, S., Gouet, P., 1993

机译：重组人丁酰胆碱酯酶G390V，氟化物-2变体，表达中国仓鼠卵巢细胞，是一种低亲和力变异

Novel Human Butyrylcholinesterase Variants: Toward Organophosphonate Detoxication

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